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Gene News

Follow hot news stories and seminal publications in the fields of genetic engineering, synthetic biology, gene therapy, and exciting new applications for gene synthesis across all disciplines of life science. Check this page weekly for featured stories curated by our Ph.D. technical writers, accompanied by the background info you need to understand how trending technologies can inform your research.

To see how GenScript is helping researchers accomplish important breakthroughs, search our Peer-Reviewed Citations. GenScript is the world's leading biotech company, offering services for Gene Synthesis, GenEZ Custom Cloning, Gene Variant Libraries, and more.

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How gut microbes influence neutrophils and exacerbate sickle cell disease and septic shock

Gut microbes influence neutrophil aging and exacerbate sickle cell disease and septic shock. A study recently published in Nature provides new evidence that gut microbes influence the immune system – in this case, by causing neutrophils to enter a pro-inflammatory "aged" state that exacerbates sickle cell disease and septic shock. Clinical studies of children with SCD revealed that daily penicillin – normally prescribed to control infection – also reduced the number of aged neutrophils in circulation, which could prevent sickle-cell crisis and chronic tissue damage.

How does the gut microbiome influence circulating neutrophils? Gut microbes secrete signals that pass through the intestinal lining into the bloodstream and activate neurophils via signaling pathways that include toll-like receptor and myeloid differentiation factor 88. These neutrophils take on a "aged" phenotype that includes enhanced αMβ2 integrin activation and enhanced pro-inflammatory activity that promotes tissue pathology.

GenScript offers molecular biology services to accelerate your research:

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Zhang D. et al. Neutrophil ageing is regulated by the microbiome. Nature. 2015 Sep 24;525(7570):528-32. doi: 10.1038/nature15367. Read the Full Text

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What the latest BRCA1 court ruling means for research and the role of gene patents in medicine

What the latest BRCA1 court ruling means for research and the role of gene patents in medicine On October 7, 2015, Australia's High Court ruled invalid the BRCA1 gene patent held by Myriad Genetics, finding that naturally-occurring DNA sequences – including mutations associated with disease – cannot be patented. This new ruling is consistent with a 2013 decision by the US Supreme Court and suggests the end of gene patents on a global scale. Researchers, biotech leaders, and patient advocacy groups are all weighing in on how this legal decision will affect the development of, and patient access to, new diagnostics that screen for genetic risk factors for disease.

The US Supreme Court's 2013 decision notes that "Patent protection strikes a delicate balance between creating "incentives that lead to creation, invention, and discovery" and "imped[ing] the flow of information that might permit, indeed spur, invention." They find that, while Myriad did discover the precise location and genetic sequence of BRCA1 and BRCA2, there was no "new and useful composition of matter" to fulfill the requirements of patent eligibility.

The NIH and numerous professional organizations have issued statements supporting the US Supreme Court's 2013 ruling on gene patents; as NIH Director Francis Collins writes, "The right to control exclusively the use of a patient's genes could have made it more difficult to access new tests and treatments." In contrast, a statement from the Biotech Industry Organization notes that "companies that research, develop and use modern biotechnology to produce products ranging from life-saving medicines and vaccines to renewable fuels, industrial enzymes and disease-or pest-resistant crops…have long relied on patents on preparations of DNA molecules and other biological chemicals in order to bring innovative, socially beneficial products to the marketplace."

While patent protection undoubtedly spurs biotechnology business investment, narrowing the scope of patents may avoid the risk that patents can stifle innovation. A recent analysis of gene patents published in Nature Biotechnology discusses differences in the uses of patented gene sequences in medicine versus crop-based agriculture, and show that patented human gene sequences map to homologous regions in diverse plant species extremely frequently, highlighting the need to narrow the scope of gene patentability, among other efforts to stimulate biological innovation across different industries and fields of study.

To accelerate your research on the human disease genetics or synthetic biology for any application, GenScript offers:

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US Supreme Court – Opinion on Association for Molecular Pathology v. Myriad Genetics – Decided June 13,2013.

cDNA ORF Clone News book

Statement by NIH Director Francis Collins on U.S. Supreme Court Ruling on Gene Patenting.

cDNA ORF Clone News book

BIO Statement On U.S. Supreme Court Review Of Isolated DNA Patents.

cDNA ORF Clone News book

Gene Patent Practice across plant and human genomes. Jefferson et al. Nature Biotechnology 33, 1033–1038 (2015) doi:10.1038/nbt.3364

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Sonogenetics: new method for non-invasive deep brain activation

new method for non-invasive deep brain activation A new technique reported in Nature Communications may make it easier and safer to activate neuronal activity in deep brain regions for both research and therapeutic uses. The approach is somewhat similar to optogenetics, which uses light to stimulate photo-activatable receptors. But by employing low-frequency ultrasound, which can travel through the body without any scattering, sonogenetics allows greater precision and deeper tissue penetration from a non-invasive stimulus.

The TRP-4 channel in C. elegans was used as a proof-of-principle to demonstrate the power of sonogenetics. This mechanosensory ion channel is normally unaffected by ultrasound, but the researchers were able to use gas-filled microbubbles to transduce the ultrasound waves and make TRP-4 channels respond to them. Then, by expressing TRP-4 in neurons that don't normally express it, researchers were able to activate both sensory neurons and interneurons with low-pressure ultrasound. Sonogenetics could be used for diverse applications – potentially even for medical applications, since ultrasound is already widely used for medical sonography.

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Ibsen et al. Sonogenetics is a non-invasive approach to activating neurons in Caenorhabditis elegans. Nature Communications, 2015; 6: 8264 DOI: 10.1038/ncomms9264 Read the Full Text

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From fertilized oocyte to embryo: genes that drive early human development identified

scientists discover genes that drive human development from oocyte to embryo A new study in Nature Communications shines a spotlight on the earliest stages of human development – from fertilized oocyte to zygote and then to day 3 embryos containing up to 10 cells. Using novel techniques for single-cell sequencing, researchers created a precise inventory of mRNA transcripts at different developmental stages. To their surprise, they found that a majority of highly upregulated transcripts in the early transition from oocyte to four-cell embyro actually map not to known coding regions but to unannotated genomic regions – which are hot new candidates for novel factors that could be extremely valuable to stem cell research going forward.

They also deduced from studying the far 5' end of transcripts that the master regulators that guide gene expression changes critical for embryogenesis are Alu elements and PRD-like homeobox genes.

These findings will inform future research on embryogenesis and infertility, as well as basic stem cell research and clinical applications such as reprogramming iPS cells for regenerative medicine. GenScript offers molecular biology services to accelerate your research:

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Töhönen et al. Novel PRD-like homeodomain transcription factors and retrotransposon elements in early human development. Nat Commun. 2015 Sep 11;6:8207. doi: 10.1038/ncomms9207. Read the Full Text

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Wild blueberries may help fight gum disease

polyphenols in wild blueberry extract fight bacteria that cause dental plaque & periodontitis A new study finds that polyphenols that occur naturally in wild blueberry plants can inhibit the growth of bacteria that cause gum disease. F. nucleatum proliferates and forms biofilms in our mouths – what we know as dental plaque – which can lead to gingivitis and periodontitis. Polyphenol-rich wild blueberry extract acts not only as an antibacterial, but also quells the inflammatory response that makes gum disease so painful. Researchers are working to develop a method to deliver these antibacterial, anti-inflammatory polyphenols to the gum in between dental cleanings in order to avoid the development of periodontitis. Since periodontitis is typically treated with conventional antibiotics, this new move could reduce antibiotic use, which helps prevent the development of antibiotic resistance among the bacterial communities that make up our oral microbiome.

GenScript offers molecular biology services to accelerate your research:

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Ben Lagha et al. Wild Blueberry (Vaccinium angustifolium Ait.) Polyphenols Target Fusobacterium nucleatum and the Host Inflammatory Response: Potential Innovative Molecules for Treating Periodontal Diseases. J Agric Food Chem. 2015 Aug 12;63(31):6999-7008. doi: 10.1021/acs.jafc.5b01525. Read the Full Text

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Working long hours increases risk of stroke & heart disease

long work hours carry health risks – increased rate of stroke & heart attack A systematic review and meta-analysis published in the Lancet finds that people who work 55 hours or more per week have a 33% higher stroke incidence, and 13% increase in relative risk of coronary heart disease, compared to those who work a standard 35-40 hour work week.

This study has already sparked heated discussion in the popular media and among scientists. While many feel that the expansive dataset from over 600,000 patients from across the world presents a strong case that these effects are real, others caution, as always, that correlation does not equal causation. And while some insist this study indicates a dire need for better public health measures to spread awareness of vascular risk factors in the workforce, others think policy impact will be negligible as long work hours have become a cultural norm in many competitive professional fields that are exempt from labor regulations.

To help you get more out of each hour you spend in the lab, GenScript offers molecular biology services to accelerate your research:

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Kivimäki et al. Long working hours and risk of coronary heart disease and stroke: a systematic review and meta-analysis of published and unpublished data for 603 838 individuals. Lancet. 2015 Aug 19. pii: S0140-6736(15)60295-1. doi: 10.1016/S0140-6736(15)60295-1 Read the Full Text

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Alternative splicing boosts brain size

A new paper published in Science shows how a single mammalian-specific exon-skipping event drives widespread changes in splicing that drive neurogenesis in big-brained mammals like humans. Read More »

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New species of ancient human, Homo naledi, discovered

A remarkable cache of over 1,500 fossils in a South African cave has revealed a new member of the hominin family. Read More »

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New 3D tissue model reveals the gene that keeps moles benign

p15 tumor suppressor protein in skin moles prevents progression to melanoma Although most moles on our skin are benign, these common bumps sometimes transform into melanoma, one of the deadliest forms of cancer. A recent study in Cancer Discovery identifies the critical gene that keeps the common oncogenic BRAF(V600E) mutation in check in moles:  the CDKN2B gene encodes the p15 tumor suppressor protein, which can halt cell proliferation via TGFβ. The paper also demonstrates a new in vivo melanoma model, derived from human skin grafts, that accurately reproduces the 3D tissue architecture of moles.

GenScript offers molecular biology services to help you uncover molecular mechanisms of cancer biology in your research:

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McNeal et al. CDKN2B loss promotes progression from benign melanocytic nevus to melanoma. Cancer Discov. 2015 Jul 16. pii: CD-15-0196. Read the Full Text

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Turning 'bad' energy-storing white fat into 'good' calorie-burning brown fat

White adipose converts to brown adipose with adrenergic stress New research shows for the first time in humans that white adipose tissue can undergo a change to resemble brown fat, which burns calories. The paper published in Cell Metabolism found that adrenergic stress in burn patients led to fat "browning" as measured by enriched UCP1, mitochondrial density, and metabolic rate. These molecular mechanisms may be harnessed to develop drugs that help prevent and treat obesity and metabolic disease.

GenScript offers molecular biology services to help you uncover molecular mechanisms of disease in your research:

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Sidossis et al. Browning of Subcutaneous White Adipose Tissue in Humans after Severe Adrenergic Stress. Cell Metab. 2015 Aug 4;22(2):219-27. Read the Full Text

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Genes that drive cancer drug resistance revealed by CRISPR-based transcription activator

CRISPR-based transcription activator A CRISPR-based research tool has identified dozens of genes that enable cancer drug resistance – including both known genes such as EGFR and new GPCRs. The dCas9-based Synergistic Activation Mediator (SAM) complex robustly activates transcription of endogenous genes using guide RNA to target the complex to any genomic locus of interest. A genome-wide library of guides enabled SAM to perform unbiased screening of genes whose activation gives rise to a phenotype of interest such as drug resistance.

SAM offers several advantages compared to a traditional approach of overexpression from cDNA. First, SAM activates endogenous gene transcription, which better allows it to capture mutations/variants in the specific primary cell or cell line in hand, as well as the complexity of transcript isoform variance. In addition, SAM avoid the difficulty of cloning large cDNA sequences into size-limited expression vectors, as well as the cost and complexity of synthesizing and using pooled cDNA libraries. And compared to previously reported CRISPR-based transcription activators, SAM shows more consistent, robust activation of genes and has been validated not only for a small subset of genes but in fact across the entire human genome.

To aid your research, GenScript offers:

*GenScript's CRISPR reagents are designed by Feng Zhang's laboratory and offered through a license with the Broad Institute.

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Konermann et al. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nat Methods. 2014 Aug;11(8):783-4. Read the Full Text

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Reversing Kidney Fibrosis by targeting EMT genes

renal fibrosis can be reversed by inhibiting EMT genes Chronic kidney disease affects 26 million Americans, and when it progresses to renal fibrosis it requires dialysis or kidney transplantation. A new study in Nature Medicine reports that the expression of just two genes involved in epithelial-to-mesenchymal transition, Twist1 and Snai1, can recapitulate the fibrotic disease state of tubular epithelial cells; even more exciting, inhibiting Twist1 and Snai1 reverses chronic renal injury in mouse models of renal fibrosis.

To help you discover and characterize genes that drive kidney disease phenotypes and that may be game-changing therapeutic targets, GenScript offers:

To assist your genome editing efforts, GenScript offers CRISPR reagents designed by Feng Zhang’s laboratory and offered through a license with the Broad Institute:

*GenScript's CRISPR reagents are designed by Feng Zhang's laboratory and offered through a license with the Broad Institute.

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Lovisa et al. Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis. Nat Med. 2015 Aug 3. doi: 10.1038/nm.3902. Read the Full Text

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Can you trust your transgenic mouse? Passenger mutations cause more trouble than previously recognized

bioregent validation is critical for reproducible research After years of backcrossing your transgenic mice, is it possible that the phenotypic effects you're studying are artifacts of strain differences and not truly caused by your gene of interest? A new study in Immunity asserts that passenger mutations that are conserved throughout backcrossing confound interpretation of all genetically modified congenic mice.

Fortunately, there’s a faster and more foolproof way to manipulate mouse genomes: CRISPR genome editing is now a mature technology with hundreds of peer-reviewed studies demonstrating its use to create heritable, homozygous knock-out or knock-in mice within a single generation. Best of all, CRISPR shows unprecedented specificity and efficiency, with no need to back-cross, allowing you to start using fully-validated new transgenic mouse strains within weeks instead of years.

To assist your genome editing efforts, GenScript offers CRISPR reagents designed by Feng Zhang’s laboratory and offered through a license with the Broad Institute:

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Vanden Berghe et al. Passenger Mutations Confound Interpretation of All Genetically Modified Congenic Mice. Immunity. 2015 Jul 21;43(1):200-9. doi: 10.1016/j.immuni.2015.06.011.Read the Full Text

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Unvalidated bioreagents are the #1 cause of irreproducible results

bioregent validation is critical for reproducible research Biomedical research is expensive – making it all the more important to carefully design and execute experiments that yield reproducible results. A recent study published in PLoS Biology found that half of all preclinical research spending in the US – over $28.2 billion/year – is lost to unreproducible studies that delay the discovery of life-saving therapies.

The study identified four primary sources of error, the most common of which is faulty biological reagents and reference materials. The authors recommend best practices to improve the efficiency of biomedical research spending, such as having funders and publishers require PIs to document reagent validation.

GenScript makes it easy to obtain reliable, validated bioreagents with ISO 9001 quality assurance certification. All DNA constructs from GenScript are sequence-verified with 100% accuracy guaranteed, and accompanied by sequence chromatograms, plasmid maps, and COA documentation to prove it.

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Freedman LP, Cockburn IM, and Simcoe TS. The Economics of Reproducibility in Preclinical Research. PLoS Biology June 2015. DOI: 10.1371/journal.pbio.1002165 Read the Full Text

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A needle-free Ebola vaccine could prevent a future epidemic

ebola vaccine research A new paper in the Journal of Clinical Investigation shows that a single dose of an aerosolized Ebola vaccine protects against subsequent lethal challenge with the Ebola virus in rhesus macaques. If these results hold up in human clinical trials, it could be a boon for people living in the remote areas such as those where last year's Ebola epidemic originated, as inhaled vaccines can be administered without the medical training required for injectable vaccines.

This is the first time an aerosolized vaccine has been designed to target a filovirus; the vaccine itself consists of an Ebola glycoprotein packaged in a human parainfluenza viral vector. To support research to characterize viral antigens and design vaccines, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

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Meyer et al. Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses. J Clin Invest. 2015. doi:10.1172/JCI81532. Read Full Text

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Cornell undergraduates seek crowdfunding for synthetic biology outreach & education programs

Cornell iGEM team synthetic biology outreach & education Cornell students participating in the international Genetically Engineered Machine (iGEM) competition are bringing underprivileged youth into the world of science research and showing the public how synthetic biology solves real-world problems.

Inside the lab, the Cornell iGEM team is developing bacterial probiotics to keep fisheries healthy. Outside the lab, they volunteer as mentors to get children exited about biology and teach a hands-on synthetic biology crash course to high school students. While the team's reagent costs have been covered by sponsorship from GenScript and other supporters, they're now seeking crowd-funding to cover remaining project costs.

Learn more about their projects and donate to their crowdfunding campaign »

GenScript is proud to sponsor iGEM teams from around the globe for the 7th year in a row. Read about the projects and awards of GenScript-Sponsored teams » GenScript's molecular biology services enable iGEM teams to create new biological building blocks and to recombine modular genetic parts into optimized synthetic gene circuits.

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Newly engineered antibiotics kill drug-resistant pathogenic bacteria

biosynthetic pathway engineering creates new antibiotics effective against erythromycin-resistant bacteria As pathogenic bacteria acquire resistance to common antibiotics, researchers are racing to discover or engineer new drugs. A recent paper in Science Advances reveals the power of modular engineering of biosynthetic pathways to create valuable new compounds. By assembling different combinations of tailoring enzymes, they created 42 new analogs of erythromycin, 3 of which are effective against erythromycin-resistant bacteria.



To support your metabolic engineering projects, GenScript offers:

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Zhang G et al. Tailoring pathway modularity in the biosynthesis of erythromycin analogs heterologously engineered in E. coli. Science Advances 2015 May; 1(4):e1500077 Read the Full Text

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New links between gut microbes and mental health in children

gut microbes and mental health As we learn more about the human microbiome, evidence keeps mounting that the 'Gut-Brain Axis' enables our intestinal bacteria to influence our mood and mental health:

  • A recent study in Brain, Behavior, and Immunity finds that differences in gut microbiome composition are associated with differences in temperament in healthy toddlers.
  • A new study in Pediatric Research finds an association between early probiotic intervention and the risk of neuropsychiatric disorders (ADHD and Asperger syndrome) later in childhood.
  • A new review discusses new evidence from epidemiology an animal studies on bidirectionality of gut-brain communication across development and efforts to prevent or treat psychological disorders by modifying intestinal flora.

To support your studies of genes – human or microbial – and their influence on human health and disease, GenScript offers molecular biology services including Gene Synthesis and CRISPR genome editing.

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Christian et al. Gut microbiome composition is associated with temperament during early childhood. Brain, Behavior, and Immunity, 2015; 45: 118 DOI: Read the Full Text

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Keightley et al. Pathways in gut-brain communication: evidence for distinct gut-to-brain and brain-to-gut syndromes. Aust N Z J Psychiatry. 2015 Mar;49(3):207-14. Read the Full Text

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Partty et al. A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial. Pediatr Res. 2015 Jun;77(6):823-8. doi: 10.1038/pr.2015.51. Read the Full Text

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Positive selection in the human genome points to Alzheimer's disease origins

Alzheimer's disease genes in human genome evolution A new method for analyzing genomes to identify marks of positive, negative, and balancing selection that occurred over the past 500,000 years have filled in new details in the story of human evolution. The genes that underwent positive selection around the time that modern humans diverged from Neanderthals are primarily involved in brain function, including several genes involved in Alzheimer's disease pathology, such as SPON1, MAPT, SORL1, ELAVL4, SNCA and SHC3. The authors speculate that natural selection favoring enhanced cognitive abilities – as these positively-selected alleles enhanced synaptic connectivity and functional plasticity – may have come at the price of vulnerability to neurodegenerative disease in aging brains, which is uniquely observed among modern humans and not other primate relatives.

To support your studies of genes and signaling pathways involved in nervous system development, physiology, and disease, GenScript offers molecular biology services including Gene Synthesis and CRISPR genome editing.

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Zhou H D et al. A Chronological Atlas of Natural Selection in the Human Genome during the Past Half-million Years. bioRxiv. 2015 May http://dx.doi.org/10.1101/018929. Read the Free Full Text

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Validating "predicted" regulatory elements through CRISPR editing of the non-coding genome

CRISPR Cas9 genome editing of the non-coding genome CRISPR/Cas9-mediated genome editing is not only an efficient way to create gene KO & KI, but is a uniquely powerful tool to functionally characterize the >98% of the genome that does not encode protein. A new study demonstrates how CRISPR can be used to systematically validate putative regulatory elements described by the ENCODE and EPIGENOME projects: even in a repeat-rich genomic region, a genomic insulator upstream of mouse tyrosinase was efficiently deleted or inverted, with no significant off-target effects and high efficiency in vivo, demonstrating a functional role for this noncoding region in regulating tyrosinase gene expression and mouse coat pigmentation.

GenScript makes it easy for your lab to start using CRISPR to create transgenic animals or isogenic cell lines.  Our license with the Broad Institute and our extensive in-house experience making CRISPR-edited mammalian cell lines enable us to make your transition to CRISPR seamless:

  1. Brush up on CRISPR principles with webinars, protocols & FAQs
  2. CRISPR gRNA constructs just ¥23,880/clone, including gRNA design & cloning into any vector!
  3. Instant ordering of guide RNAs specifically targeting any mouse or human gene
  4. Complementary custom design of gRNA for any target in any species – request it here.
  5. Choose from vectors developed in Feng Zhang's laboratory, including all-in-one and improved GeCKO lentiviral vectors – FREE when you order gRNA constructs.
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Seruggia D et al. Functional validation of mouse tyrosinase non-coding regulatory DNA elements by CRISPR–Cas9-mediated mutagenesis. Nucleic Acids Res. 2015 May 26;43(10):4855-67. Read the Free Full Text

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Fly genes reveal how 'morning people' & 'night owls' differ

Chronotype diversity associated with differential gene expression far broader than circadian clock genes It’s well-established that being a ‘morning person’ or a ‘night owl’ is more than a simple preference – “chronotype” or diurnal preference has a biological basis, and it carries consequences for risk of diabetes, depression, insomnia and other diseases.

Humans aren't the only animals who show chronotype diversity: a recent study comparing early vs late chronotype fruit flies identified 152 differentially expressed genes that cluster into highly evolutionarily conserved pathways such as MAPK and Hedgehog, suggesting that the circadian clock may control cascades of gene expression that set larks and owls on distinct developmental trajectories.

To support your research needs, GenScript offers Gene Synthesis services to allow you to study the function of genes in isolation or in complex signaling pathways that underlie neurodevelopment, circadian physiology, behavior, and disease risk.

  • Gene synthesis starting at ¥26/bp
  • Economic Cloning: choose from 77 free vectors to get expression-ready clones
  • Express Mutagenesis – any mutation in any sequence - starting at $99/mutant clone
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Pegoraro M. et al. Gene expression associated with early and late chronotypes in Drosophila melanogaster. Front. Neurol. (2015) Read Free Full Text

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Oncolytic viruses gain momentum

Oncolytic virus such as new HSV virotherapy can be combined with antibody immunotherapies for cancer treatment With the first oncolytic virus poised for FDA approval, and several more in pharma pipelines, the arsenal of cancer therapeutics may soon gain a powerful new tool: viruses that seek & destroy tumor cells and that stimulate anti-tumor immune responses. An oncolytic HSV-based therapy has shown impressive efficacy in advanced melanoma, and may be even more potent when combined with antibody immunotherapies or cell therapies.

Engineering oncolytic viruses and therapeutic antibodies relies upon cutting-edge molecular biology. As a pioneer in gene synthesis, GenScript accelerates research to develop novel cancer therapeutics and uncover basic mechanisms of tumor biology.

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Dolgin E. Oncolytic viruses get a boost with first FDA-approval recommendation. Nature Reviews Drug Discovery 14, 369–371 (2015) Read Full Text

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Therapeutic antibody engineering: new study reveals unintended consequences

therapeutic antibody engineering of IgG Fc domainAntibody engineering is a critical strategy for developing next-generation IgG1-based therapeutics for cancer and inflammatory diseases. But a recent study in J. Immunology provides clear new evidence of the challenge of optimizing one feature of a rAb without disrupting other clinically vital functions.

To extend the half-life of therapeutic IgG, this study used Gene Synthesis to generate a panel of novel Fc mutants designed to optimize the pH-dependent FcRn–IgG1 interaction. The engineered Fc variants showed either enhanced or reduced Fc-mediated effector functions, as shown by binding to C1q and FcγRs as well as downstream cellular processes measured by ADCC and other cell-based assays.

To support your research needs for therapeutic protein engineering or any area of biomedical research, GenScript offers:

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Grevys et al. Fc Engineering of Human IgG1 for Altered Binding to the Neonatal Fc Receptor Affects Fc Effector Functions. J Immunol. 2015 Jun 1;194(11):5497-508. doi: 10.4049/jimmunol.1401218. Read Full Text

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Sweet-tasting Proteins: a healthier alternative to sugar or artificial sweeteners?

protein engineering of monellin sweet protein For the many people who strive to reduce sugar intake, it can be tough to choose between natural sugars, artificial low-calorie sweeteners, or denying the craving for sweets. Proteins may offer a better solution: did you know that some naturally-occurring proteins taste hundreds of times sweeter than sugar? Plants native to West Africa naturally produce sweet proteins, such as monellin, isolated from the “serendipity berry” Dioscoreophyllum cumminsii and miraculin, isolated from the “miracle fruit” Synsepalum dulcificum.

A recent paper shows how structure-guided protein engineering enabled the design of new protein-based low-calorie sweeteners that could be used in food – potentially offering a powerful tool to combat increasing rates of diabetes and obesity.

To support your research needs, GenScript offers Gene Synthesis services to accelerate protein engineering, structural and biochemical studies, or characterizing novel variants in vitro or in vivo.

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Rega et al. Design of sweet protein based sweeteners: Hints from structure–function relationships. Food Chem. 2015 Apr 15;173:1179-86. doi: 10.1016/j.foodchem.2014.10.151. Read Full Text

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Cheese-making microbes: new biomarker genes track microbial community metabolism

cheese microbes, microbial community meta-omics Do you know that dozens of different species of bacteria, yeast, and other microbes work together to make cheese? Surface-ripened cheese microbial communities came under the meta-omics microscope in a recent paper published in PLoS ONE, producing a vivid picture of the metabolic activities and cross-talk between different organisms that takes place over the month-long process of cheese maturation. For example, they showed that robust growth of two yeast strains early in the process causes an increase in pH in cheese curds, which promotes later growth of acid-sensitive bacteria. The study also revealed the species and metabolic pathways primarily responsible for lactose degradation that allows cheese to be enjoyed by many of us who are lactose-intolerant. Most exciting, meta-transcriptomics analysis identified new gene biomarkers that could be used in the future to monitor and improve the efficiency and safety of food fermentation – with delicious results.

To support your research needs, GenScript offers Gene Synthesis services to allow you to study gene function and to engineer novel enzymes and metabolic pathways.

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Dugat-Bony et al. Overview of a Surface-Ripened Cheese Community Functioning by Meta-Omics Analyses. PLoS One. 2015 Apr 13;10(4):e0124360. Read Full Text

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New class of orthogonal regulators of gene expression: STARs

RNA binding DNA to regulate gene expression Small regulatory RNAs abound in nature, and they're proving to be a versatile tool for programming novel synthetic gene networks to precisely control gene expression. Naturally-occurring sRNAs can repress or enhance translation by interacting with ribosome binding sites (RBSs), and can repress transcription by binding intrinsic terminator hairpins. However, there are no known naturally-occurring sRNAs that could activate transcription, which limits the ways in which synthetic gene regulatory circuits can be designed.

A recent paper in Nature Chemical Biology reports on the development of small RNA transcriptional activators (STARs), a newly-engineered functional class of small RNA that expands the capabilities for RNA-only logic gates. In addition to designing sRNAs with potent transcriptional activation (up to 94-fold enhancement), they systematically deduced design rules to allow other researchers to create customized sRNAs for any application in the future.

GenScript offers Gene Synthesis and library design and construction services to allow you to apply synthetic biology tools to any research project.

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Chappell et al. Creating small transcription activating RNAs. Nature Chemical Biology 2015 Mar;11(3):214-20. doi: 10.1038/nchembio.1737. Read Full Text

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Ancient genes lead modern antibiotic-resistance arms race

antibiotic resistance gene The arms race between pathogenic microbes and the antibiotics we used to control them continues to rage: few new drug candidates are in the pipeline to tackle enterobacter and MRSA, and new reports show that diverse bacteria trade the genes that confer antibiotic resistance more easily than previously imagined.

Overuse of antibiotics is often considered to be the primary selective pressure that prompts bacteria to acquire, maintain, and spread genes conferring antibiotic resistance, but a new study suggests that these genes pre-date the emergence of modern medicine. The microbiota of people living in an isolated Venezuelan tribe (that had never been exposed to antibiotics) carry genes conferring antibiotic resistance, suggesting ancient roots to a very modern problem.

To support your research needs, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

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Clemente et al. The microbiome of uncontacted Amerindians. Science Advances 01 Apr 2015: Vol. 1 no. 3 e1500183. DOI: 10.1126/sciadv.1500183 Read Full Text

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How tall will your children be? New evidence that epigenetics tune complex quantitative traits

Epigenetics Egfr Traits like height, which seem to vary in an intractably complex quantitative manner, may actually be regulated in a very straightforward way by simple epigenetic mechanisms. A new study published in Nature Communications reports that global DNA methylation levels determine body size in carpenter ants. The degree of methylation of the Egfr gene was identified as the critical regulator of ant body size, consistent with EGFR's role as a transcriptional regulator for many genes involved in growth signaling. Other polygenic traits may similarly be coordinated by master regulators whose expression can be quantitatively tuned by epigenetic modification in response to environmental conditions.

To accelerate your studies of epigenetics and gene variation, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

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Alvarado et al. Epigenetic variation in the Egfr gene generates quantitative variation in a complex trait in ants. Nat Commun. 2015 Mar 11;6:6513. Read Full Text

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A universal "DNA regulatory code" governs protein-DNA interactions

Transcription factor binding, protein DNA interaction Although protein coding regions are highly conserved across evolution, regulatory regions differ greatly between species, which enables diverse gene expression patterns that allow flies and humans to develop into very different animals. Transcription factor proteins in different species might be expected to differ somewhat in how they bind DNA, but a new systematic comparison of drosophila, mouse, and human finds that TF binding specificity is almost perfectly conserved through 600 million years of divergent evolution. This surprising result, that transcription factors have not evolved to recognize even subtly different DNA motifs, implies that gene expression is regulated by a single universal "DNA regulatory code" that governs protein-DNA interactions.

To generate a collection of 760 DNA-binding domains for systematically assaying drosophila transcription factor binding specificity, these researchers used codon-optimized gene synthesis from GenScript. GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

To support your research needs, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

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Nitta et al. Conservation of transcription factor binding specificities across 600 million years of bilateria evolution. Elife 2015 Mar 17;4. Read Full Text

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Dad's DNA is favored in gene expression: pervasive bias toward paternal alleles discovered

DNA maternal paternal allele Although we inherit DNA from two parents in equal proportions, a new report in Nature Genetics reveals a pervasive bias in gene expression favoring paternal alleles. Genetic imprinting and parent-of-origin effects have been observed before, but this study identifies hundreds of new genes that show allelic imbalance, highlighting the importance of heritable variation in regulatory regions of the genome.

This finding was made possible by crossing highly divergent mouse strains through a breeding experiment called the Collaborative Cross. This project aims to expand genetic diversity in mouse models to more closely resemble the degree of genetic variation found within the human population, in order to gain more insight into the genetics of human diseases.

To support your research needs, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

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Crowley et al. Analyses of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic imbalance. Nat Genet. 2015 Apr;47(4):353-60. Read Full Text

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Exome sequencing study finds a new ALS-causing gene and shifts the spotlight to autophagy

ALS motor neuron A new study published in Science tackles the mystery of the genetic basis for ALS, a motor neuron disease in which 90% of cases are sporadic and the vast majority of those show no mutations in genes known to cause familial ALS. Through whole-exome sequencing of thousands of ALS patients and controls, researchers were able to identify a new ALS-causing gene, TBK1, and to show that disruptions to the autophagy pathway play a more important role in ALS than previously recognized.

As next-generation sequencing expands access to collections of new gene variants associated with disease such as the ALS and control exome sequence banks created in this study, a critical next step for developing diagnostics and therapeutics is to characterize how these mutations contribute to disease processes.

To support your research needs for customized DNA constructs encoding novel gene variants, GenScript offers Gene Synthesis services to create any gene sequence in any vector, with 100% sequence accuracy – because you have more important things to do than routine cloning.

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Cirulli et al. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science. 2015 Mar 27;347(6229):1436-41. Read Full Text


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Potent new HIV "vaccine" bypasses the immune system: new fusion immunoadhesin binds Env & blocks infection

HIV DNA A new study published in Nature provides striking new evidence that an immunoadhesin gene therapy approach could provide effective, long-term protection against HIV-1 – perhaps sooner and better than a conventionally-developed vaccine. Unlike traditional vaccines, which introduce an immunogen in order to stimulate a person's immune system to produce antibodies in response, this approach essentially replaces the need for an immune system response to HIV. Instead, it involves stably expressing an immunoadhesin, which acts similarly to a monoclonal antibody in binding and neutralizing a pathogen. CD4-Ig immunoadhesins have been used in HIV research for several years, but this new study finds that fusing CD4-Ig to a small CCR5-mimetic sulfopeptide allows it to bind the HIV-1 envelope glycoprotein Env far more potently than CD4-Ig alone or any of the best broadly neutralizing antibodies studied to date. Furthermore, this study shows that AAV-expressed eCD4-Ig provided longstanding protection against SIV challenges in rhesus macaques and is a promising candidate for safely and effectively protecting human populations from HIV.

Read the full publications »

To support your research needs for customized DNA constructs for vaccine research, therapeutic antibody engineering, and immunology, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

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Gardner et al. AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges. Nature. 2015 Mar 5;519(7541):87-91. Read Full Text


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The race to map cannabis genomes for "personalized" medical marijuana

cannabis gene Plant genetics researchers are now racing to map the genomes of many varietal strains of cannabis in order to better understand the genetic variations underlying widely varying levels of THC and CBD. These efforts aim to address the need for reliable dosing and quality control in cannabis plants grown for medicinal use and may also help bring the power of personalized medicine to cannabinoid-based therapies.

Amid continued controversy over medical marijuana policies – for example, The New England Journal of Medicine just published a perspective on the public health risks – researchers are discovering more potential therapeutic uses for cannabis-derived compounds. In addition to its wide use for pain relief and anti-emesis, new reports show cannabis-based drugs can kill tumor cells, and in a mouse model of Alzheimer 's disease they decrease Aβ42 levels and protect against cognitive decline.

To support your research needs for customized DNA constructs for disease research and comparative genomics, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

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Aso et al. Cannabis-Based Medicine Reduces Multiple Pathological Processes in AβPP/PS1 Mice. J Alzheimers Dis. 2015;43(3):977-91. Read Full Text

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Scott et al. The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Mol Cancer Ther. 2014 Dec;13(12):2955-67. Read Full Text

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Hernandez D. How genetics is reshaping the marijuana industry. Fusion 4 Feb 2015. Read Full Text

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Ghosh et al. Medical Marijuana's Public Health Lessons — Implications for Retail Marijuana in Colorado. N Engl J Med 2015 Mar 12;372(11):991-3. Read Full Text

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Nelson B. Medical marijuana: Hints of headway? Despite a conflicted regulatory landscape, support for medical marijuana is growing amid increasing evidence of potential benefits. Cancer Cytopathol. 2015 Feb;123(2):67-8. Read Full Text


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DNA minicircles: a new tool for safe gene delivery and earlier cancer detection

cancer oncogenesis tumor gene A new study in PNAS reports the development of a safe, reliable, and sensitive method for earlier cancer detection. Rather than looking for endogenous cancer biomarkers that may be present in the blood, researchers engineered a novel, genetically-encoded biomarker: the tumor-specific PSurv promoter drives tumor-specific expression of human SEAP, a secretable reporter gene that can be easily detected. Using mice, they found that their engineered biomarker accurately distinguished between tumor-bearing and tumor-free individuals, and even quantitatively reported on tumor burden. In order to facilitate use of this diagnostic tool in humans, they selected an unusual but uniquely safe vector: DNA minicircles.

DNA minicircles are safer than other types of vectors for gene delivery for several reasons. First, they avoid the many safety concerns of viral vectors such as replication competence, immune reactions, and insertional mutagenesis inciting pathology such as oncogenesis. Even compared to traditional nonviral plasmid vectors, minicircles are less immunogenic because they completely lack antibiotic resistance genes or a prokaryotic backbone that may be recognized as foreign by the human immune system. Furthermore, minicircles have higher gene transfer rates and longer-lived expression profiles than other non-viral vectors, making them a highly effective vehicle as well. MCs have recently become much faster and less expensive to produce, making them a promising vehicle for future gene therapy efforts.

To support your research needs for customized DNA constructs to engineer novel biomarkers, to deliver tumor-targeted gene therapy, or to study cancer signaling pathways, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

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Ronald et al. Detecting cancers through tumor-activatable minicircles that lead to a detectable blood biomarker. Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):3068-73. Read Full Text


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A cure for glioma: nanoparticles deliver gene + pro-drug to brain

glioma cancer biology A new study by researchers at Johns Hopkins reports stunning results for curing glioma in rats, using a new method likely to be safe and effective in humans. In order to make the pro-drug ganciclovir effective at killing glioma cells in the brain, DNA encoding HSVtk must be delivered to the brain, ideally without using viral vectors for gene delivery. Instead, they selected biodegradable nanoparticles which they showed could permeate through the brain via intracranial convection-enhanced delivery. This is the first time that nanoparticle-delivered therapeutics have effectively killed brain cancer cells and extended survival in animals.

To support your studies of molecular and cellular features of neuropsychiatric diseases, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

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Mangraviti et al. Polymeric Nanoparticles for Non-Viral Gene Therapy Extend Brain Tumor Survival In Vivo. ACS Nano. 2015 Feb 24;9(2):1236-49. Read Full Text


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New Research links childhood stress and psychiatric disease to premature cellular aging

chromosome telomere cellular aging A new study in Biological Psychiatry finds hallmarks of cellular aging in people who have experienced early life stress, depression, anxiety, or substance abuse. The relationship seen between psychopathology and shortened telomeres confirmed earlier reports, and this paper presents the first evidence of altered mitochondrial biogenesis, including increased mtDNA copy number, in people with early life stress, anxiety, or substance use disorders.

To support your studies of molecular and cellular features of neuropsychiatric diseases, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

avian genome, bird gene Tyrka et al. Alterations of Mitochondrial DNA Copy Number and Telomere Length with Early Adversity and Psychopathology.
Biological Psychiatry. Article in Press; Published Online: January 16, 2015. DOI: http://dx.doi.org/10.1016/j.biopsych.2014.12.025 Read Full Text

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How and why did flying birds' genomes become so small?

Avian genome, bird gene Bird genomes tend to be considerably smaller than the genomes of other vertebrates, and a new Science paper from the avian genome consortium sheds light on the mystery of how and why bird genomes became so trim.

Not only have avian lineages lost transposable elements (<10% of bird genomes are repeats, compared to 34-53% in mammals), but even their protein coding regions show shorter introns and intergenic regions. This genomic contraction is also seen in bats, the only group of mammals that fly -- a case of convergent evolution suggesting that flight creates a selective pressure on genomes to shrink.

Some have proposed that the sheer mass of so many copies of junk DNA in all the body's cells, and the energetic demand of maintaining it, was too costly for flyers to maintain. Phylogenetically controlled correlations have been observed between genome size and relative flight muscle size as well as other morphologic features, suggesting that the metabolic intensity of powered flight has driven genome size reductions in birds (Wright et al. 2014). Others have suggested that introns, which play a role in regulating gene expression, may shrink in flying birds due to a need for more rapid gene regulation in response to the intense energetic demands of powered flight (Zhang et al. 2014). On the other hand, some researchers suggest that small genomes first evolved in the saurischian dinosaur lineage long before avian flight appeared, casting doubt on flying behavior as a driver of genome size (Organ et al. 2007).

To support your studies of genes, intergenic regions, and genome structure in any species, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

gene news book Zhang et al. Comparative genomics reveals insights into avian genome evolution and adaptation.
Science. 2014 Jul;46(7):748-52. Read Full Text

gene news book Wright et al. Metabolic 'engines' of flight drive genome size reduction in birds. Proc Biol Sci. 2014 Jan 29;281(1779):20132780. Read Full Text

gene news book Organ et al. Origin of avian genome size and structure in non-avian dinosaurs. Nature. 2007 Mar 8;446(7132):180-4.
Read Full Text

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Human microbiome research sheds light on psychiatric disease

microbiome gut-brain axis On the search for gene variants underlying psychopathology, a recent article in the Harvard Review of Psychiatry discusses the lack of success of GWAS and GxE studies to pinpoint genetic determinants of depression. But new findings reveal that our gut microbes are critical players in determining susceptibility to depression, anxiety, and other psychiatric disorders; for example, numerous publications report that antibiotics and probiotics influence CNS disease symptoms. Ongoing studies like the crowd-sourced American Gut project aim to gather meta-genomic data on microbiome populations – opening new frontiers to study the biological basis of mental illness.

To support your studies of gene variants and gene-environment interactions in health and disease, GenScript offers Gene Synthesis services to provide the custom DNA constructs you need with 100% sequence accuracy.

gene news book Wang & Caspar. The role of microbiome in central nervous system disorders. Brain Behav Immun. 2014 May;38:1-12.
Read Full Text

gene news book Dunn et al. Genetic determinants of depression: recent findings and future directions. 2015 Jan-Feb;23(1):1-18. 2014 May;38:1-12. Read Full Text

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A New Method to Map Mosaic Mutations in the Brain

brain mosaic mutations Did you learn long ago that every cell in your body contains an identical copy of your DNA? In fact, a growing body of evidence shows that mosaicism occurs more frequently than we thought – and new technology is making it possible to detect de novo mutations in specific cell lineages and understand how they impact our health.

A study in Neuron reports a new method for single-cell whole-genome sequencing to identify somatic mutations and map their mosaic patterns in the brain. And, as a Nature Genetics paper reports, searching for somatic mutations can help identify the cause of, and potential treatments for, certain elusive diseases; learn how novel mutations in KCNH1 were identified as the cause of a rare seizure disorder in children whose mothers were healthy mosaic carriers.

To support your studies of gene variants and their functions in health and disease, GenScript offers Gene Synthesis services to provide the custom clones you need with 100% sequence accuracy, starting at just ¥26/bp.

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How do birds learn to sing? Surprisingly like the way humans learn to speak

birdsong geneStudies recently published in Science reveal that songbirds learn to sing using largely the same set of genes and brain pathways used in humans speech – a remarkable new account of convergent evolution in two quite distant lineages. Further work on the classic model songbird, the zebra finch, fleshes out the story of two-way communication between genes and singing behavior, showing that 10% of the avian genome is regulated by singing behaviors via activity-dependent transcription factors and epigenetic modifications. This rich new understanding of the molecular, anatomical, and functional basis of songbird vocalization was made possible by recent publication of 45 new bird genome sequences, which will open new frontiers for future studies in comparative genetics.

For your studies of gene function and regulation of gene expression in any species, GenScript offers Gene Synthesis and Economic Cloning services to accelerate your research.

gene news book Pfenning et al. Convergent transcriptional specializations in the brains of humans and song-learning birds. Science. 2014 Dec 12;346(6215):1256846. Read Full Text
gene news book Whitney et al. Core and region-enriched networks of behaviorally regulated genes and the singing genome. Science. 2014 Dec 12;346(6215):1256780. Read Full Text

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Finally discovered: the gene variant that make some people natural blondes

hair color gene; human gene variant Although blonde hair color clearly runs in families, the genetic variant that gives rise to platinum locks has only recently been discovered. A study published in Nature Genetics follows up on previous GWAS findings to identify the critical SNP and how it functions. A single base pair change in the enhancer region of the KITLG gene reduces binding by the transcription factor LEF1, which alters growth factor signaling in developing keratinocytes – and lightens fur color in mice harboring the human variant.

As you work to uncover the genetic basis of phenotypic variation, GenScript is here to provide custom gene synthesis to accelerate studies of gene function and regulation of gene expression.

gene news book Guenther et al. A molecular basis for classic blond hair color in Europeans. Nat Genet. 2014 Jul;46(7):748-52. Read Full Text

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DNA in space: genes are functional after a trip to space and back

astrobiology, DNA in space A recent paper in PLoS ONE reports that the building blocks of life can remain biologically functional after a trip to space and back. Plasmid DNA applied to the outside of a sounding rocket survived the microgravity of space and the intense heat (exceeding 128℃ ) and pressure (hypergravity of 17.6 g) during atmospheric re-entry. This suggests that DNA, or other biomolecular markers of extraterrestrial life, could survive entry through Earth's atmosphere embedded in meteorites. This has huge implications for life on Earth and elsewhere in the universe; traces of DNA left by humans on "space junk" could complexify our search for signs of life elsewhere in the universe.

To support your studies of life here on Earth, GenScript offers Gene Synthesis services with the unmatched expertise to create any gene in any vector – even difficult DNA sequences containing high or low GC content, repeats, or secondary structures.

gene news book Thiel et al. Functional Activity of Plasmid DNA after Entry into the Atmosphere of Earth Investigated by a New Biomarker Stability Assay for Ballistic Spaceflight Experiments PLoS One. 2014 Nov 26;9(11):e112979. Read Full Text

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CRISPR genome editing in human cells: improved targeting with the H1 promoter

CRISPR genome editing A recent paper in Nature Communications reports success with a clever technique to make CRISPR-mediated genome editing easier in human cells. Compared to the commonly-used U6 promoter, driving guide RNA expression from the H1 promoter more than doubles the number of targetable sites within the genomes of humans and other eukaryotes.

Why is H1 more versatile than U6? The U6 promoter initiates transcription from a guanosine (G) nucleotide, while the H1 promoter can initiate transcription from A or G. In designing a gRNA sequence, the requirement for the protospacer adjacent motif (PAM) sequence "NGG" at the end of a 20-mer means that U6-driven gRNA must fit the pattern GN19NGG. But H1-driven gRNAs can also target sequences of the form AN19NGG, which occur 15% more frequently than GN19NGG within the human genome.

To support your genome editing efforts, GenScript offers:

gene news book Ranganathan et al. Expansion of the CRISPR–Cas9 genome targeting space through the use of H1 promoter-expressed guide RNAs. Nat Commun. 2014 Aug 8;5:4516. Read Full Text

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Changing T-cell receptor specificity through in vitro engineering

T-cell protein engineering A recent paper in Nature Communications reports a breakthrough that could make T-cell therapeutics much faster and easier to develop: in vitro-directed evolution of T-cell receptors enable researchers to change the peptide specificity of T-cells without having to isolate T-cell clones. Starting with predictions regarding key residues within the complementarity determining regions (CDRs), researchers generated and screened mutant libraries to identify a novel TCR protein variant that recognizes a cancer peptide of interest, MART1/HLA-A2.

GenScript offers comprehensive services to support your protein engineering efforts, from gene synthesis to High-throughput Protein Variant expression and purification, Antibody Library & Phage Display and Functional Assay Validation.

gene news book Smith et al. Changing the peptide specificity of a human T-cell receptor by directed evolution. Nat Commun. 2014 Nov 7;5:5223. Read Full Text

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Turning E. coli into tape recorders with genome editing

e. coli synthetic biology A recent paper in Science reports a revolutionary method to enable E. coli to create robust, rewriteable records of biological events through precise dynamic genome editing. A programmable module called SCRIBE translates input signals into ssDNA fragments that can be inserted into genomic DNA and securely stored until it is read, edited, or erased later on. This new breakthrough in synthetic biology effectively harnesses the stable, high-capacity information reservoir represented by the genome to serve as flexible, analog storage for any customized use.

To help you generate novel DNA modules or synthetic genes, GenScript offers leading gene synthesis technologies and unparalleled services that all deliver 100% sequence-perfect plasmid DNA clones:

gene news book Farzadfard F, Lu TK. Genomically encoded analog memory with precise in vivo DNA writing in living cell populations. Science. 2014 Nov 14;346(6211):1256272. Read Full Text

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Scorpion Peptide keeps pests off rice crops

agricultural engineering; codon-optimized genes for plant biology Efforts are ongoing to develop new crop varieties that produce greater yields when grown without chemical pesticides, which can harm the environment and are expensive for farmers to purchase and apply. A recent paper in Plant Science reports that rice plants' natural defenses against pests can gain a boost from a scorpion peptide to keep leafroller pests at bay.

Codon-optimized gene synthesis can promote the efficient expression of transgenes in plants for both basic and applied research. For example, a Dec 2014 paper in Plant Science reports that rice plants' natural defenses against pests can gain a boost from a scorpion peptide to keep leafroller pests at bay. This study used codon-optimized gene synthesis services from GenScript to express the scorpion peptide gene LqhIT2 in rice plants in order to study how it affected the plant and its lepidopteran pests in both the lab and the field. In addition to direct species-selective toxicity, LqhIT2 boosted jasmonate-mediated phenylpropanoid biosynthesis in the rice plants, which produces lignin and flavonoids that are critical components in plant defense. This finding could lead to the development of new rice varieties that produce greater yields when grown without chemical pesticides.

GenScript offers free codon optimization with our patented OptimumGene™ algorithm to help you improve soluble protein expression in your experiments. Our gene synthesis services allow you to get 100-% sequence-verified expression clones containing any custom-made DNA sequence starting at ¥26/bp, with cloning into any vector starting at $49.

gene news book Tianpei et al. Scorpion peptide LqhIT2 activates phenylpropanoid pathways via jasmonate to increase rice resistance to rice leafrollers. Plant Sci. 2014 Dec (1-11); 2014-12. Read Full Text

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Synthetic HCV genome engineered with mutations enabling in vitro infectivity:
an important new tool to support HCV research and vaccine development

in-vitro virus research; infectious cell culture As HCV-related liver disease claims hundreds of thousands of lives each year, Hepatitis C Virus research has thus far been hampered by a lack of infectious cell-culture systems to support basic and translational research including vaccine development. A new paper in J.Virology reports a breakthrough in developing in vitro infectious clones for the most common HCV strains. These researchers synthesized HCV-1 and H77 prototype genomes containing specific mutations that enable infectious particle production in cell culture.

To make viral genome synthesis faster and more affordable, GenScript's new GenBrick™ synthesis service leverages efficient one-step assembly technology.

gene news book Li et al. Efficient infectious cell culture systems of the hepatitis C virus prototype strains HCV-1 and H77. J Virol. 2014 Oct 29. pii: JVI.02877-14. Read Full Text

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Control gene expression with your thoughts:
Harnessing brain activity to tune gene and cell therapies

mind-controlled gene expression; optogenetics; synthetic biology A new paper in Nature Neuroscience sounds like science fiction: humans can control protein expression from "designer cell" implants with only their thoughts. An EEG reads brain wave patterns associated with certain mental states, and a brain-computer interface wirelessly transmits a signal to cell cultures or to cells implanted in lab animals. This study used synthetic gene circuits to create a light-inducible orthogonal signal transduction pathway leading to tunable expression of a target protein. This application of synthetic biology holds great promise for gene and cell therapies that could revolutionize patient care.

Optogenetics and other types of synthetic gene circuits are increasingly used in neuroscience research. GenScript's gene synthesis services provides any DNA construct you need with 100% sequence accuracy. Our new GenBrick™ synthesis service makes it easier than ever to get sequence-perfect long genes or entire genetic circuits.

gene news book Folcher et al. Mind-controlled transgene expression by a wireless-powered optogenetic designer cell implant. Nature Communications. 2014 Nov 11;5:5392. Read Full Text

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Paper-based gene circuits allow an Ebola sensor to be developed in a single day

synthetic biology, gene circuit A new paper in Cell reports a breakthrough technique to bring synthetic biology out of the lab. By freeze-drying biological components and embedding them in paper, researchers can rapidly create new cell-free transcription-based detectors that can be used anywhere, without relying on laboratories with sterile cell culture facilities. As a proof-of-principle, they developed a paper-based Ebola virus detector in a single day.

To enable studies requiring custom-made genetic circuits or synthetic genomes, GenScript's new GenBrick™ synthesis service leverages efficient one-step assembly technology to produce 8-15kb long DNA building blocks for synthetic biology, offering 100% sequence-perfect clones in just 23 business days for $0.45/bp. Compared to the time-consuming and error-prone process of assembling oligos and screening for mutation-free clones in your own lab, GenScript's GenBrick™ synthesis service saves you time, money, and hassles.

gene news book Pardee et al. Paper-Based Synthetic Gene Networks Cell. 2014 Nov 6. 159(4):940–954. Read Full Text

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Guinea Pig enzyme may fight cancer better than current drugs
Tumor-killing L-asparaginase finally characterized, 60 years later

guinea pig enzyme; animal research for drug development After a 1953 paper revealed that guinea pig serum could kill tumor cells through L-asparaginase activity, several bacterial L-asparaginases were developed as FDA-approved drugs to treat acute lymphoblastic leukemia (ALL) and other cancers. However, side effects persist, likely due to off-target glutaminase activity and immunogenicity. The first problem could be addressed by identifying or engineering an enzyme with better substrate specificity, while immune reactions against the bacterial enzymes may be circumvented by using a mammalian enzyme. So researchers recently went back to the original source: the guinea pig. 60 years after that first report, they've now characterized a guinea pig enzyme they say could potentially replace currently used cancer drugs. They report the first crystal structures for gpASNase1, both ligand-free and in complex, which help explain the lack of off-target L-glutaminase activity in this enzyme compared to bacterial homologs currently in therapeutic use.  They also determined that the guinea pig enzyme has superior kinetic properties compared to the human enzyme; while the kinetics have made the human enzyme a poor candidate for therapeutic use, the guinea pig enzyme has favorable kinetic properties similar to those of bacterial homologs currently in use clinically.

In order to express and purify bacterial and mammalian L-asparaginases for enzymatic and structural assays, these researchers ordered codon-optimized gene synthesis from GenScript. See how GenScript can accelerate your research:

  • Gene Synthesis starting at only ¥26/bp for 100% sequence-verified clonal DNA
  • Free Codon Optimization with our patented OptimumGene™ algorithm boosts soluble protein expression 100-fold.
  • New Economic Cloning Service – get expression-ready clones for just $49 and 2 days added to your gene synthesis order.
gene news book Schalk AM, Nguyen HA, Rigouin C, Lavie A. Identification and Structural Analysis of an L-asparaginase Enzyme from Guinea Pig with Putative Tumor Cell-killing Properties. J Biol Chem. 2014 Oct 15. pii: jbc.M114.609552. Read Full Text

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Can chocolate improve your memory?
Flavanols found in chocolate may prevent normal memory loss with aging

synaptic plasticity, memory, hippocampal synapse The dentate gyrus within the hippocampus is thought to be involved in age-related memory decline. A new study in Nature Neuroscience reports that healthy older adults who consumed a high-flavanol diet for three months showed improved function in both fMRI scans and DG-specific cognitive tests.

In order to study the mechanisms of age-related memory decline and the neuroprotective effects of flavanols, GenScript's gene synthesis service makes it easy to obtain 100% sequence-verified DNA constructs. For example, Codon-optimized gene synthesis is routinely used to create optogenetic reporters for noninvasive imaging of synaptic networks even in deep brain regions such as the dentate gyrus.

  • Learn more about how GenScript's gene synthesis services accelerate neuroscience research
  • Visit us at booth #1113 at the Society for Neuroscience meeting in Washington DC, Nov 15-19.
gene news book Brickman AM et al. Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults. Nature Neuroscience, 2014 Oct 26. doi: 10.1038/nn.3850. Read full publication

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Link between high-carb diet and fat gain can be broken
New research discovers genes linking metabolic pathways in a surprising way

obese mouse, obesity research model It's been well established that a high-sugar diet can lead to fat accumulation and weight gain. A new study finds this effect disappears when there's a loss of function in alh-6, a mitochondrial enzyme involved in proline metabolism.1 Alh-6 deficiency activates SKN-1/Nrf2, which induces fatty acid oxidation genes – the first demonstrated link between amino acid metabolism and lipid metabolism, and one that is conserved from worms to humans.

This enhanced fat-burning tendency isn't always good – for example, in C. elegans under conditions of nutrient deprivation, alh-6 mutants lost weight quickly and didn't survive as well. And the harms of a high-sugar diet may extend beyond weight gain to accelerating cellular senescence, according to a recent study that showed shortened telomeres in humans after sugary soda consumption.2 However, this new finding does holds promise for preventing or treating metabolic diseases such as obesity and type II diabetes, especially because Nrf2 activators are already in development for safe use in humans as cytoprotective agents under electrophilic stress.

To study the physiological effects of altering the expression of key metabolic enzymes and transcription factors regulating broad, conserved homeostatic programs, GenScript's gene synthesis service makes it easy to obtain 100% sequence-verified plasmids encoding WT ORFs or any mutation or fusion construct you can design. We offer:

  • Gene Synthesis starting at only ¥26/bp for 100% sequence-verified clonal DNA
  • New Economic Cloning Service – get expression-ready clones for just $49 and 2 days added to your gene synthesis order.
  • Industry-leading Codon Optimization to boost heterologous protein expression; learn more by joining our free live webinar on Wednesday 10/30.
gene news book 1. Pang S et al. SKN-1 and Nrf2 couples proline catabolism with lipid metabolism during nutrient deprivation. Nat Commun. 2014 Oct 6;5:5048.
gene news book 2. Leung CW et al. Soda and Cell Aging: Associations Between Sugar-Sweetened Beverage Consumption and Leukocyte Telomere Length in Healthy Adults From the National Health and Nutrition Examination Surveys. American Journal of Public Health. 2014 Oct 16:e1-e7.

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Building bigger DNA: 3D DNA structures on nanometer scale

3D DNA biomaterials In addition to its familiar function of encoding genetic information, DNA is a valuable biomaterial for fabricating customized nanostructures. DNA's ability to self-assemble into precise 3-D structures used in applications from drug delivery to electronic components. A new study reports the creation of scaffolded DNA origami structures far larger than previously described, thanks to two major technological improvements: the use of longer DNA scaffolds and the use of a new chip-based platform for inexpensive synthesis of 1600 DNA sequences serving as staples.

GenScript has developed chip-based DNA synthesis technology to power our GenPlus™ High-Throughput Gene Synthesisservice. As the global leader in gene synthesis, with over 13 years of R&D innovation and customer satisfaction, our technologies can deliver any custom DNA sequences you can imagine, of any length & complexity, with 100% sequence accuracy guaranteed starting at just ¥26/bp.

gene news book

Marchi et al. Toward larger DNA origami. Nano Lett. 2014 Oct 8;14(10):5740-7. Read Full Text


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Coffee Genome Sequenced
Exploring the genes inside our favorite beans

coffee genome, caffeine biosynthesis In addition to providing a much-loved beverage, the coffee plant is emerging as a valuable model organism for research on the evolution of biosynthetic pathways and genome structure. A recent Science publication presents the newly-sequenced coffee genome and a stimulating case of convergent evolution: caffeine biosynthesis evolved independently in coffee, tea, and cacao.

This study also examined the coffee genome structure and found a unique pattern of gene family expansions among N-methyltransferases (NMTs) involved in multiple biosynthetic pathways. New versions of old genes appear to have arisen through tandem sequential duplication, unlike in other members of the asteroid angiosperm lineage which have experienced whole-genome triplication. This unique feature of coffee sheds new light on the mechanisms by which enzyme function diversification occurs.

To study novel genes and non-coding regions that are discovered in newly-sequenced genomes, GenScript's gene synthesis service makes it easy to obtain 100% sequence-verified plasmids and other custom molecular biology reagents. We offer:

Further Reading:

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Ebola Update: siRNA-based therapeutic drug moves forward

ebola virus, siRNA therapeutics The WHO has released new projections that the death-toll for the current Ebola outbreak will reach 20,000 by November, bringing increased attention to the need to contain the spread of this epidemic and to reduce the 70% death rate. Prevention efforts are focused on public health campaigns to reduce transmission rates, and two Ebola vaccine candidates are poised to enter clinical trials soon. Several patients diagnosed with Ebola appear to have benefitted from treatment with the siRNA-based drug TKM-Ebola, in addition to other therapies such as blood transfusions from Ebola survivors and supportive care. TKM-Ebola made two major steps forward this week:

  • Tekmira won FDA authorization under expanded access protocols to offer the investigational drug TKM-Ebola to patients diagnosed with or suspected to be infected with Ebola.
  • TKM-Ebola may enter expedited clinical trials in West Africa. An International consortium has received £3.2 Million from the Wellcome Trust to establish Ebola Virus Disease (EVD) treatment centers that will administer clinical trials using one or more investigational therapeutics under consideration, among which RNAi has been prioritized.

Tekmira is developing the RNAi-based therapeutics that can be delivered using lipid nanoparticle (LNP) delivery technology. Preclinical studies of TKM-Ebola were published in The Lancet in 2010. Read the Full Publication » Lipid-encapsulated siRNA delivery has also shown promise for treating Marburg Virus infection (J. Infect. Dis. 2013)

Work continues to develop new therapeutic strategies for Ebola and other deadly viruses. CDC researchers recently developed a new system for identifying antiviral agents that are effective against Marburg and Ebola viruses, using codon-optimized Ebola virus genes synthesized by GenScript. Read the free full text of the paper »

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Making photosynthesis more efficient

plant genetics, plant genome editing Photosynthesis is such a fundamentally important process that you might think plants are highly efficient at it. However, scientists working to improve crop yields have noticed that one enzyme, Rubisco, represents a weak link in the photosynthetic pathway due to its poor oxygenase activity and slow turnover. A recent paper in Nature reports that plants can be engineered to use a better Rubisco enzyme from cyanobacteria, which increases carbon fixation rates. Tobacco plans whose native Rubisco gene was completely knocked out were able to grow by using transgenic cyanobacterial Rubisco, which successfully assembled into active enzyme to support autotrophic photosynthesis. The next step will be to introduce the remaining components of the cyanobacterial CO2 concentrating mechanism, including inorganic carbon transporters and carboxysome shell proteins, to recapitulate a complete and functional CCM in plants. If this strategy is successful in increasing total photosynthesis rates and thus improving crop yields, it could be a major breakthrough for sustainable farming and global food security.

Plant biologists are increasingly turning to CRISPR-mediated genome editing to create knock-in and knock-out strains, for several reasons. CRISPR is highly efficient with very low risk of off-target effects. It is easy to use in any lab, and compatible with widely-used methods for creating transgenic strains through agrobacterium-mediated transformation. However, CRISPR technology does not leave a “transgenic” footprint if the Cas9 and gRNA constructs are transiently expressed or are backcrossed out. Therefore there are hopes that new plant strains created using CRISPR/Cas9 genome editing technology may escape being labeled as GM strains which may increase their acceptance as food crops. Learn more about how gene synthesis and genome editing are being used in plant biology research applications.

GenScript is the global leader in gene synthesis to accelerate genetic engineering, CRISPR-mediated genome editing, recombinant enzyme expression, biosynthetic pathway engineering, and gene functional studies. We offer:

gene news book Lin MT, Occhialini A, Andralojc PJ, Parry MA, Hanson MR. A faster Rubisco with potential to increase photosynthesis in crops. Nature. 2014 Sep 25;513(7519):547-50. Read Full Text

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Engineering yeast to be morphine factories: A step forward for sustainable drug production

yeast engineering, metabolic engineering, synthetic yeast genome In addition to serving as a model organism for basic biology research, such as in the cutting edge work being done by the synthetic yeast genome project, yeast are increasingly being adapted through metabolic engineering to be used for industrial applications. A recent paper in Nature Chemical Biology reports the successful biosynthesis in yeast of medically important opioids.1 To reproduce part of the complex alkaloid metabolic pathway in yeast, the researchers had to engineer yeast to express multiple biosynthetic enzymes that naturally occur in poppy and bacteria. Their first efforts were thwarted by low product yields owing to undesired side reactions that diverted intermediates away from the intended biosynthetic pathway. Fortunately they developed a clever solution: by localizing certain enzymes to the ER, they were able to compartmentalize key reactions within the cell. Their persistence paid off, leading to yields of up to 131 mg/L of opioid products, the highest yield of desired metabolite ever reported from genetically engineered micro-organism.

Other studies of metabolic engineering inyeast and alkaloid biosynthesis have employed codon-optimizedsynthetic genes from GenScript. GenScript is the global leader in genesynthesis to accelerate recombinant proteinexpression, metabolic engineering, or any projects requiring gene over-expressionor genetic modification.

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Thodey K et al. A microbial biomanufacturing platform for natural and semisynthetic opioids Nature Chemical Biology 2014 Oct;10(10):837-44. Read Full Text


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New class of DNA Topoisomerases found
Implications for the history of protein evolution and the future of cancer therapeutics

DNA topoisomerase A recent paper in Nucleic Acids Research reports the discovery of a new class of Type II DNA topoisomerase enzymes, found in archaeal and bacterial genomes as well as bacterial plasmids. As their name suggests, topoisomerases help to solve topological problems that arise when complementary DNA strand separate to allow transcription, replication, or some forms of DNA repair.

This study used computational techniques to mine genomic data in order to identify novel genes containing domains with high similarity to previously-known topoisomerase-encoding genes. They identified never-before-seen genes that encode type IIB enzymes in which the A and B subunits are fused into a single polypeptide, forming the smallest known type IIB enzymes. This monophyletic group of newly discovered enzymes differs substantially from other archaeal and eukaryotic type IIB enzymes, prompting a proposal to classify them into a new subfamily called DNA topoisomerase VIII. Functionally, they show diverse DNA relaxation, decatenation and cleavage activity, meriting further characterization.

In the puzzling story of how topoisomerase enzymes originated and diversified over evolutionary history, this study provides new evidence that topoisomerases diversified in the Viral/Plasmid world before entering the three domains of living cells, and independently entered multiple bacterial, archaeal, and eukaryotic lineages on different occasions – and may still be doing so. The current pool of “mobile elements” represent potential reservoirs of novel proteins involved in DNA metabolism that could be harnessed by efforts toward protein engineering for biomedical and synthetic biology purposes. Furthermore, the Paenibacillus host in which one of the new topoisomerase genes was found may be a promising source for novel topoisomerase inhibitors that could be therapeutic candidates for cancer.

Read the full publication »

To biochemically characterize these novel enzymes, these researchers used GenScript's gene synthesis service to obtain 100% sequence-verified plasmids for recombinant protein expression and purification. GenScript offers custom molecular biology services to accelerate your research:

  • Gene synthesis starting at only ¥26/bp for 100% sequence-verified clonal DNA
  • New Economic Cloning Service – get expression-ready clones for just $49 and 2 days added to your gene synthesis order.

References

  1. Gadelle et al. DNA topoisomerase VIII: a novel subfamily of type IIB topoisomerases encoded by free or integrated plasmids in Archaea and Bacteria. Nucleic Acids Res. 2014 Sep 1;42(13):8578-91. Read Full Text
  2. Dinh et al. DNA topoisomerase 1α promotes transcriptional silencing of transposable elements through DNA methylation and histone lysine 9 dimethylation in Arabidopsis. PLoS Genet. 2014 Jul 3;10(7):e1004446. Read Full Text.
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Mitochondrial DNA mutations, including pathogenic heteroplasmies, are surprisingly common

mitochondria, mtDNA mutation, heteroplasmy Each cell in the human body contains only two copies of genes stored in nuclear DNA, but can contain thousands of copies of genes found in mitochondrial DNA (mtDNA). Mutations in mtDNA can accumulate over your lifespan and contribute to diverse pathologies including neurodegenerative disease, cancer, and diseases associated with aging. A new study employing deep sequencing of 1,000 human genomes reports that healthy humans harbor mutations in their mitochondrial DNA at a surprisingly high rate: 90% of healthy individuals carry at least 1 mtDNA heteroplasmy, and 20% of apparently healthy people carry known pathogenic mtDNA mutations.1

How many copies of a pathogenic mtDNA mutation are needed to tip the scales from health to disease? The consensus seems to be that about 60% of all mitochondria in a cell must harbor a mutation before deleterious phenotypes can be observed. In most cases, a mutation causes a loss of function that can be compensated for by the remaining normal copies of the gene. However, some gain of function mutations may cause problems at much lower doses.

Can mtDNA mutations be corrected to prevent disease? A recent study in EMBO Mol Med. reports a new techniques for correcting mtDNA mutations utilizing mitochondrially-targeted zinc finger nucleases.2 If developed for clinical use, techniques like this may provide a way to intervene to remove potentially harmful mtDNA heteroplasmies before disease onset. Other gene therapy strategies such as codon-optimized gene delivery or genome editing with CRISPR/Cas9 technology are being used extensively for basic and translational research.

GenScript offers gene synthesis of customized DNA constructs – giving you ultimate flexibility to design mutants, promoter-reporters, fusion proteins, or any other constructs you can imagine to help you study pathogenic mutations and the function of genes and pathways involved in mitochondrial disease etiology & progression.

References

  1. Ye et al. Extensive pathogenicity of mitochondrial heteroplasmy in healthy human individuals. Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10654-9. Read Full Text
  2. Gammage et al. Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations. EMBO Mol Med. 2014 Apr;6(4):458-66. Read Full Text
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Human genome update: What % of DNA serves a biological function?

human genome, chromosome, jnk DNA Long-standing controversy surrounds the question of how much of the human genome is functional and how much can rightly be dismissed as “Junk DNA.” A recent publication in PLoS Genetics sheds new light on the composition of the human genome, and demonstrates that different classes of genomic elements show different rates of change.

By comparing modern genomes of different species, scientists observe that some portions of the human genome have accumulated mutations at a much slower than expected rate. This suggests that when mutations have occured, they've had a negative effect on fitness and been purged from the population. A new study shows that ~8.2% of the human genome appears to be currently subject to purifying selection, and therefore serving some function that contributes to fitness.1

To put this number in context, it is much smaller than the 80% of the genome has been annotated by the ENCyclopedia Of DNA Elements (ENCODE) consortium as having some biochemical activity2. However, it is almost 8 times the amount of the human genome that encodes protein, and more than 3x larger than the amount of evolutionarily constrained human genome shared with mouse. This is consistent with the observation that certain classes of genomic sequences, especially long non-coding RNA (lncRNA), have high ‘turnover’ rates, meaning that they have likely gained and lost function relatively rapidly throughout the human lineage, compared to low-turnover observed within protein-coding regions.3

Why does it matter? Portions of the genome that bear signatures of purifying selection but whose functions are not yet understood may represent fields ripe for exploration to discover novel genes or novel elements that regulate gene expression, chromosomal stability, or other key biological processes. Conversely, portions of the genome that appear to be non-functional relics of evolution could be candidates for omission in efforts to create sleeker synthetic genomes in cells engineered for industrial/biomedical applications, as is being done through the Sc2.0 synthetic yeast genome project.

To help your research into the mysteries of the genome, GenScript offers:

References

  1. Rands CM et al. 8.2% of the Human genome is constrained: variation in rates of turnover across functional element classes in the human lineage. PLoS Genet. 2014 Jul 24;10(7):e1004525. Read Full Text
  2. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012 Sep 6;489(7414):57-74. Read Full Text
  3. Palazzo AF, Gregory TR. The case for junk DNA. PLoS Genet. 2014 May 8;10(5):e1004351. Read Full Text
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Will CRISPR bring us more nutritious fruit crops without GM worries?

CRISPR nutrition food security biofortified crops Global nutrition and food security are major concerns as human population rises and the land area devoted to agriculture shrinks. Biotechnology has accelerated the development of improved food crops that can address these issues in order to boost the economic productivity of farms and improve human health. However, genetically modified food crops have met with consumer resistance and increasing regulation due in part to concerns over the long-term safety and environmental effects of transgenes being introduced into plants. One way in which the scientific community is responding is to identify new technologies that can achieve the nutrition and food security goal of prior genetic engineering efforts while avoiding the use of transgenes and the “GM” label that is controversial among consumers.

“Superbananas” have made news headlines as a biofortified crop containing enhanced levels of vitamin A to counteract widespread vitamin A deficiencies in certain parts of the world. A new “Science & Society” paper in Trends in Biotechnology presents the argument that luxury items such as fruit crops may find more consumer acceptance for bioengineering than do staple crops such as grain and rice, and discusses the possibility that new technologies such as CRISPR-mediated genome editing may elude the regulatory designation as “GMOs” since they contain no foreign DNA.1 Successful CRISPR-mediated genome editing has been demonstrated in citrus fruits2 and a variety of other food crops and diverse plant species3.

GenScript offers gRNA constructs for CRISPR-mediated genome editing, including expert gRNA design for any species.

References

  1. Nagamangala K et al. Looking forward to genetically edited fruit crops. Trends Biotechnol. 2014 Aug 12. pii: S0167-7799(14)00147-4. Read Full Text.
  2. Jia H, Wang N. Targeted genome editing of sweet orange using Cas9/sgRNA. PLoS One. 2014 Apr 7;9(4):e93806. Read Full Text.
  3. Jiang W. et al. Demonstration of CRISPR/Cas9/sgRNA-mediated targeted gene modification in Arabidopsis, tobacco, sorghum and rice. Nucleic Acids Res. 2013 Nov 1;41(20):e188. Read Full Text.
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Could CRISPR technology be used to cure AIDS and other devastating viral diseases?

HIV DNA Why are viral diseases like AIDS still incurable? Although antiretroviral drugs can effectively control viral load in many patients, the permanent integration of viral DNA into a host genome means that patients remain vulnerable to re-activation of a latent virus. Exciting new research now shows that CRISPR technology can remove HIV DNA that has integrated into the host genome in human cells, re-igniting our hopes for developing a true cure for AIDS.

CRISPR-mediated genome editing is revolutionizing biomedical research due to its precise targeting, high efficiency, and ease of use in any cell type or experimental system. CRISPR has been used to create new transgenic animal models for basic and translational research, and it holds promise for use in gene therapy and other medical applications.

GenScript's new GenCRISPR gRNA construct service makes it easy to perform CRISPR/Cas9-mediated genome editing in your own lab.

  • Take advantage of complimentary gRNA design by our scientists who have demonstrated expertise in gRNA design: see our functionally-validated knock-out cell lines
  • Our gene synthesis services have been cited in landmark publications in Nature Methods, Genetics, and Development by researchers who've pioneered CRISPR/Cas9 technology and applied it to new species: see references

Read the full publication: Hu et al. RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. Proc Natl Acad Sci U S A. 2014 Jul 21.

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Genetic Approaches for Cancer Treatment: Childhood leukemia can be reversed by Pax5

genetic approaches for cancer treatment, leukemia gene, cancer gene targets Researchers recently discovered that switching on the expression of Pax5, a tumor suppressor gene commonly mutated in childhood leukemia patients, was sufficient to reverse leukemia.1 As published by Liu et al. in Genes & Development, re-engaging the transcriptional program seen in normal B-cell differentiation, Pax5 restoration achieved durable disease remission despite the continued presence of other oncogenic mutations.

Numerous genes other than Pax5 are frequently mutated in leukemia and other cancers, including GSTT12, CEPBA, RUNX1, and GATA2.3 The increasing use of whole-genome sequencing of biopsied tissue from individual patients is shedding light on new gene targets every day. Given the increasing incidence of cancers worldwide, despite the advances in therapeutic modalities such as antibodies for immuno-oncology, genetic approaches to modulate gene expression levels through gene switches, or to replace mutated genes with healthy ones through gene therapy, could provide valuable additions to our anticancer arsenal.

To study gene expression and gene function, thousands of researchers around the world turn to GenScript for gene synthesis to generate custom DNA constructs encoding newly discovered genes, disease-associated gene variants, somatic and inherited mutations, and even large gene cassettes of 50kb or longer.

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Running Red Lights: Stop Codon Reassignment and Read-through

stop codon; codon reassignment Stop codons made the news in May when Science published findings about stop codons reassignments in the wild – that is, the recoding of typical stop codons to encode specific amino acids, which occurs in viral genes involved in phage-host interactions.1

Now a new study in Nucleic Acids Research addresses stop codon read-through in mammalian cells – where chromosomal genes can be expressed with C-terminal extensions that may contain functional domains.2

To study gene expression, thousands of researchers around the world turn to GenScript for gene synthesis, including the synthesis of newly discovered genes, gene variants, mutant sequences, and even entire genetic circuits of 50kb or longer.

  1. Ivanova et al. Stop codon reassignments in the wild. Science. 2014 May 23;344(6186):909-13.
  2. Loughran et al. Evidence of efficient stop codon readthrough in four mammalian genes. Nucleic Acids Res. 2014 Jul 10 [epub ahead of print].
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A new candidate drug fights glioblastoma by targeting a suite of miRNAs that regulate Wnt/β-catenin signaling

Glioma, cancer drug The small molecule BASI showed potent anti-cancer effects in a high-throughput screen for glioblastoma multiforme (GBM), the most common type of adult brain tumor. Now a new study reveals that BASI inhibits glioma proliferation, invasion, and migration in vitro and in vivo by altering levels of several micro-RNAs, which form a coordinated, multi-level blockade of the Wnt / β-catenin signaling pathway. Building upon prior work that elucidated the role of several of these miRs in regulating Wnt signaling, this study provided novel characterization of the role of miR-181d, and reported on the ability of the small molecule BASI to simultaneously target the entire suite of miRNAs that regulate β-catenin through diverse mechanisms. Because Wnt is implicated in the growth of multiple tumor types, BASI and the miRs it regulates are promising subjects for further basic and translational research.

To study the effect of miR-181d on the β-catenin pathway, these researchers ordered custom-cloned CTNNB1 and CREBBP reporter plasmids from GenScript. With GenEZ™ Molecular Cloning, it's easy to get customized ORF clones or even completely custom genes in expression-ready plasmids.

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18,000 new species discovered in the past year
Biodiversity provides insights for biomedical innovation

biodiversity, new species Mother Nature offers a gold-mine of information about how common problems have been solved across evolutionary time. Although we tend to rely on only a few model organisms in the lab, searching the genomes of other species provides valuable insights.

The International Institute for Species Exploration released its “Top 10 New Species” list on May 23rd, to celebrate the birthday of Carolus Linnaeus, the “Father of Taxonomy.” Learn more about the 10 most intriguing life-forms identified in the last year on the IISE website.

How can newly discovered species help your research?
Everyday biomedical researchers are:

  • using conserved portions of homologous genes to predict critical regulatory motifs and protein domains
  • studying how microbiota in human gut contribute to obesity
  • harnessing unusual bacteria to fight cancer

Studying genes found in a variety of species can provide key insights into gene regulation, protein function, metabolic pathways, and more. Whatever your research focus, GenScript has the tools you need.

  • Need ORFs cloned into your choice of vector? Try our GenEZ ORF cloning service, starting at ¥9,900/clone.
  • Need codon-optimized or custom genes? Gene Synthesis services start at ¥45/bp, or just ¥26/bp for orders of 25 genes or more.
  • Need custom DNA constructs fast? Express gene synthesis offers delivery in as little as 4 days.
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A One-Two Punch for Cancer: New Target + New Drug

small molecule cancer drug; low-nanomolar inhibitor; anticancer therapy; A recent study published in Nature circles around to a jackpot by shifting from a drug screen to molecular target and back – and delivers a major advance for cancer drug discovery by combining chemical proteomics, pharmacology, and genetic approaches.

Starting with a small molecule that blocks Ras-dependent cancer cell proliferation, researchers discovered an attractive new target for anticancer therapies: MTH1 (Nudt1). They used codon-optimized gene synthesis from GenScript to express Nudt1 for enzymatic assays and crystallization studies, and identified (S)-crizotinib as a highly specific, low-nanomolar MTH1 inhibitor.

How does MTH1 help cancer cells grow?

A nucleotide pool sanitizing enzyme, MTH1 helps avoid the incorporation of oxidized nucleotides during DNA damage repair and DNA replication. This is useful for all cells to protect the integrity of their DNA – but it's especially important for cancer cells due to their fast proliferation rates and high levels of intracellular reactive oxygen species. Similar to currently used chemotherapy agents that target rapidly dividing cells, drugs that inhibit MTH1 could make cancer cells selectively vulnerable to oxidative damage-induced cell death.

Why is (S)-crizotinib well-positioned for drug development?

(S)-crizotinib was discovered as a contaminant in a preparation of the (R)-enantiomer of crizotinib, which is already FDA approved for clinical use. Since the two compounds differ in only one chiral center, it is likely that (S)-crizotinib will be a safe drug with favorable pharmacokinetic and pharmacodynamic properties. Further, the chemical proteomics experiments in this study demonstrate that, while (R)-crizotinib binds to many different protein kinases, MTH1 as the only common high-significance interactor of (S)-crizotinib, and showed nanomolar potency for (S)-crizotinib to block cancer cell proliferation. This high degree of specificity and potency also increase the chance that (S)-crizotinib will pass safety and efficacy benchmarks in clinical trials.

As the most cited biotech company worldwide, GenScript is the ideal partner to accelerate your research by synthesizing the customized DNA constructs your experiments require. As a pioneer in Gene Synthesis technology, GenScript now offers GenEZ Next-Gen Molecular Cloning, the easiest way to get expression-ready, sequence-verified clones in your choice of vector, containing either ORF RefSeqs or gene insert sequences of your own design.

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DNA delivered to ear improves hearing

guinea pig enzyme; animal research for drug development Successful neurotrophin gene therapy in a guinea pig model of sensorineural deafness could soon be translated to humans. A report in Science Translational Medicine finds that electroporation of BDNF cDNA into mesenchymal cells of the ear stimulates spiral ganglion neurite regeneration, which improves sensitivity to electrical signals transmitted by cochlear implants.

Gene delivery, whether for therapeutic or basic research use, requires high-quality customized DNA constructs. Gene synthesis enables the construction of more efficient vectors and cargos for gene delivery. As a pioneer in Gene Synthesis technology, GenScript now offers GenEZ Next-Gen Molecular Cloning, the easiest way to get expression-ready, sequence-verified clones in your choice of vector.

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Long-elusive osmotic channel protein identified through genome-wide RNAi screen

membrane-bound protein, ion channel, osmotic channel A critical regulator of osmotic homeostasis has finally been identified: SWELL1, a ubiquitous membrane-bound protein, has been identified as an essential component of the volume-regulated anion channel.

How do cells maintain a constant volume despite fluctuations in osmolarity?
As we know, water diffuses freely across the semi-permeable plasma membrane of all cells, and tends to move from areas of lower solute concentration to areas of higher osmolarity. Therefore, any time intracellular osmolarity increases or extracellular osmolarity decreases, cells should swell – with disastrous consequences. But they don’t – instead, they do a remarkable job of maintaining constant cell volume, presumably by exporting ions whenever they sense their volume increasing. Scientists inferred the presence of a volume-regulated anion channel (VRAC) through which chloride ions leave swollen cells in order to restore homeostasis. Further studies characterized the pharmacological and electrophysiological properties of VRACs, but their molecular composition has remained elusive – until now.

A recent study published in Cell reports on a genome-wide RNAi screen using a cell-based fluorescence assay to identify VRAC components. The authors discovered that the ubiquitously expressed gene LRRC8A (now renamed SWELL1) encodes a transmembrane protein required for hypotonicity-induced ion flux. Expressing an RNAi-insensitive SWELL1 cDNA clone completely restored channel function, and several point mutants modulated the volume-sensitive ionic currents.

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A newly identified post-translational modification critical for learning:
δ-catenin palmitoylation mediates activity-induced synapse plasticity

synaptic plasticity, memory, hippocampal synapse Synaptic plasticity is known to underlie learning and memory, but we're still discovering the molecular mechanisms by which synaptic activity leads to changes in synapse morphology and function. A recent Nature Neuroscience paper reports a new post-translational modification that is required to coordinate the changes involved in memory formation: after enhanced synaptic activity, DHHC5 palmitoylates δ-catenin, increasing its binding to synaptic cadherin both in vitro and in the hippocampus of fear-conditioned rodents. These researchers used a synthetic δ-catenin gene, in which the palmitoylated cysteine residues were mutated to serine, to demonstrate that δ-catenin palmitoylation is required for numerous facets of activity-induced synaptic plasticity, including N-cadherin stabilization at synapses, postsynaptic spine enlargement, insertion of GluA1 and GluA2 into the synaptic membrane, and increased mEPSC amplitude.

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CRISPR enables heritable multiplex genome editing in insects
Bmku70 knockout in B. mori creates a powerful new model for studying DNA repair

CRISPR/Cas9 technology for precise gene editing has already proven successful in miceC. elegansXenopus tropicalis, and plants. Now CRISPR has been used the silkmoth Bombyx mori, an important insect model organism.

Ma et al. used CRISPR to disrupt the Bmku70 gene, which is required for non-homologous end joining (NHEJ) and plays a role in telomere length maintenance, subtelomeric gene silencing and antigen diversity. Bmku70 knockouts exhibit an increased frequency of homologous recombination and thus can provide a powerful new model for future studies on the fundamental mechanisms of DNA repair.

gene news book Ma et al. CRISPR/Cas9 mediated multiplex genome editing and heritable mutagenesis of BmKu70 in Bombyx mori. Sci Rep. 2014 Mar.

Why is CRISPR more efficient than TALEN or ZFN for insect models?

Ma et al. report that numerous prior attempts at site-directed insertion of recombinant DNA into the B. mori genome have failed. These earlier experiments used ZFN or TALEN techniques, which have effectively generated transgenic strains of many species through targeted homologous recombination (HR). However, insect cells show a preference for the nonhomologous end joining (NHEJ) pathway rather than the HR pathway for repair of double strand breaks (DSBs), making the efficiency of HR-based genome editing very low.
While both zinc-finger nucleases (ZFN) and TAL effector nucleases (TALEN) can be engineering to target a locus of interest, they rely upon protein-DNA interaction; in contrast, CRISPR uses an RNA-DNA pairing to determine the specificity and activity of the nuclease. RNA-DNA interactions are generally much more stable than protein-DNA interactions, yielding higher efficiency of success. In addition, CRISPR is much simpler and faster for researchers to use.

The CRISPR method relies upon customized gene constructs that encode a codon-optimized Cas9 nuclease and a synthetic guide RNA for precise targeting. GenScript's gene synthesis service can prepare the constructs you need for CRISPR/Cas9-based genome editing.

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Magnetic bacteria: the next breakthrough for tumor treatment?
Magnetosome genes isolated and successfully expressed in a model organism

Magnetotactic bacteria (MTB) are diverse group of gram-negative bacteria that contain specialized organelles called magnetosomes. Magnetosomes produce uniform crystals of magnetic iron compounds such as magnetite (Fe3O4) or greigite (Fe3S4), and align in chains that form a permanent magnetic dipole within the cell.

Naturally occurring MTBs are difficult to grow in the lab, so scientists sought to express magnetosomes in a more tractable model organism. However, recapitulating an entire functioning organelle isn't as simple as expressing a single transgene, especially since all the elements involved in magnetosome biogenesis and function have not been identified. Magnetosome formation and function requires numerous genes that work together to direct 1) invagination of the cytoplasmic membrane to form free-standing vesicles that will become the magnetosome organelles; 2) the uptake of iron into the new magnetosome; 3) the redox-controlled biomineralization of magenetite crystals; and 4) the self-assembly of crystals into nanochains along a dedicated cytoskeletal structure.

In a new Nature Nanotechnology paper, Kolinko et al. identify a minimal gene cassette (containing up to 29 unique genes) that can induce magnetosome biosynthesis within R. rubrum, a bacterial strain commonly used for biotechnology. Building upon earlier work by several other groups (Zurkiya et al.; Nakamura et al.; Goldhawk et al. and Benoit et al.) expressing the MagA gene in E. coli or mammalian cells and using magnetotectic bacteria in cancer imaging, this new report of engineering R. rubrum to generate magnetosomes represents an advance toward large-scale biotech and medical applications.

gene news book Kolinko et al. Biosynthesis of magnetic nanostructures in a foreign organism by transfer of bacterial magnetosome gene clusters. Nature Nanotechnology (2014) doi:10.1038/nnano.2014.13

Why do bacteria have magnetosomes? (What's the advantage of carrying around a magnet?)

Magnetosomes give MTBs a unique ability to sense electromagnetic fields, which helps them orient and migrate by either passively aligning or actively swimming along geomagnetic field lines. These cells may also be able to harness magnetic force to swim faster than other microbes: some MTBs have been observed to swim at speeds nearly twice that of E. coli cells in spite of being larger in size and in spite of having less flagellar proteins.

gene news book Yan et al. Magnetotactic bacteria, magnetosomes and their application. Microbiol Res. 2012 Oct 12;167(9):507-19. Review.

How can magnetosomes treat tumors?

Magnetosomes can be taken up by cancer cells and then exposed to a magnetic field, causing hyperthermia that slows cancer cell proliferation and eradicates tumor xenografts in mice. Magnetosomes can also serve as efficient delivery vehicles for gene vaccines and may be used to improve MRI technology by enhancing magnetic resonance contrast for medical imaging. This is only the latest example of how genetic engineering brings new advances in the prevention, diagnosis, and cure of human disease.

gene news book Search or Browse peer-reviewed papers that use GenScript's Gene Synthesis service to aid in genetic engineering

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Optogenetics goes two-channel:
New opsins Chronos and Chrimson solve the problem of how to excite distinct neuronal populations.

"Optogenetics" allow researchers to stimulate synaptic activity in specific neurons that are made to express light-sensitive ion channels (channelrhodopsins). Despite the variety of opsins with different peak wavelength sensitivities, until now it has not been possible to independently activate two distinct neural populations without significant cross-talk or losing temporal resolution. Researchers at MIT reported in Nature on two new opsins with non-overlapping excitation spectra, Chronos and Chrimson, that allow independent optical excitation of distinct neural populations in mouse brain slices. These tools open the door to explore how multiple synaptic pathways interact to encode information in the brain.

Opsin genes occur naturally in microbial algae. In order to efficiently express these genes in mammalian cells, these researchers turned to GenScript for codon optimization and gene synthesis. Codon optimization overcomes codon usage bias, secondary structures, and other sequence features that can inhibit heterologous gene expression. GenScript has developed the leading codon-optimization algorithm: OptimumGene™, patented in 2012 and continuously improved based upon the latest research findings.

gene news book Klapoetke et al. Independent optical excitation of distinct neural populations. Nat Methods. 2014 Mar;11(3):338-46.
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"Obesity Genes" – The race to discover and characterize genetic variants to fight a weighty epidemic

obese mouse, obesity research model Scientists are striving to understand how genetic variants predispose individuals to overweight and weight-related diseases such as type 2 diabetes, which are becoming more prevalent. Many genetic variants have been identified that seem to be associated with obesity – but a critical next step is to elucidate the mechanisms by which these 'mutant' sequences actually alter gene expression or protein function.

Breaking news: FTO, the first "obesity gene" to be identified and still to date the strongest genetic determinant of obesity risk, has now been shown to influence obesity only indirectly by housing regulatory elements for the true actor: the homeobox gene IRX3.

The first "obesity gene," FTO, was discovered by three unique genome wide association studies published in 2007 1, 2, 3. However, a new study published in Nature on March 20, 2014 reveals that obesity-related variants located within FTO introns have no effect on FTO gene expression or function, but instead regulate the expression of IRX3, a gene several hundred thousand base pairs away. Mechanistic studies employing both human brain tissue and transgenic mice show that IRX3 expression in the hypothalamus controls basal metabolic rate and body mass and composition.

gene news book Smemo et al. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507, 371–375 (20 March 2014).

This reversal of FTO' s reputation highlights the importance of investigating the functional roles of new genetic variants as soon as they are identified. In order to characterize the functional roles of naturally-occurring DNA mutations, researchers often need to generate variant constructs for experiments such as reporter gene assays. GenScript's mutagenesis service offers a time-saving and cost-efficient option to get the constructs you need.

With advances in genome sequencing and personalized medicine, it's more critical than ever to understand how genetic variants actually influence physiology and disease etiology. GenScript is the leading provider of custom molecular biology services including gene synthesis, which can deliver the precise DNA constructs you need, without the limitations and headaches of traditional PCR-based manipulation of pre-existing templates.

gene news book Browse recent peer-reviewed publications on obesity research

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Rare codons in the N-terminal region enhance protein expression

A recent Science paper reports that the presence of AT-rich rare codons in the N-terminal region enhances protein expression by reducing RNA secondary structure in bacteria. This is great news for all researchers whose experiments have suffered from low levels of heterologous protein expression. By taking advantage of the degeneracy of the genetic code, you can alter your nucleotide sequence to favor efficient protein expression while preserving the amino acid sequence you need – a technique called codon optimization.

It's been known for some time that codon usage bias among different species. As a consequence, when researchers want to express a gene in a different organism in order to study it – for example, expressing a human allele associated with disease in a model organism such as a mouse – the gene may be poorly expressed because a scarcity of tRNAs can cause translation to stall. One solution to this problem is to over-express the desired tRNA species – but this introduces the confound of altering the stoichiometry governing translation for every protein in the cell. A better solution is to replace codons that are rare in the host organism with more common ones. Many codon optimization algorithms have been developed upon this basis.

peptide services technical resourcesHowever, these latest results published in Science suggest that eliminating rare codons may not always be beneficial: as with real estate, it's all about location, location, location. At the N-terminus of a protein, some rare codons actually increase protein expression levels. It turns out that the key here is not tRNA abundance, but rather the fact that AT-rich codons tend to reduce the formation of mRNA secondary structures that can prevent the mRNA from progressing smoothly through the ribosome – throwing a wrench into the gears of the translation machinery.

GenScript has developed the leading codon-optimization algorithm: OptimumGene™, patented in 2012 and continuously improved based upon the latest research findings. Consistent with this study in Science, OptimumGene™ accounts for the secondary structure of mRNA and allows rarer codons at the N-terminus. GenScript's algorithm considers dozens of additional factors known to affect transcription, mRNA stability, translation, and protein folding, and generates up to 100-fold increases in protein expression.

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2014 marks the 100th anniversary of X-ray diffraction

x-ray crystallography, x-ray diffraction, crystal structure Crystallography has afforded scientists a chance to see sub-microscopic details of protein structures for a full century now. While we may take this technique for granted, it's still revealing secrets that can revolutionize our understanding of protein folding, enzyme activity, and evolution – with very real implications for protein engineering efforts that hold immense promise for applications such as biomedicine and alternative energy.

For example, in a recent paper published in Nature Chemical Biology, crystal structures reveal important features of QueE, a key enzyme in purine biosynthesis. By crystallizing QueE in complex with the catalyst AdoMet and substrates CPH4, 6CP, and CDH, they discovered that QueE contains a modified core fold unlike any other AdoMet radical enzyme. After locating the active site and characterizing its intricate hydrogen bonding network, they discovered that substrate binding generates a metal-binding site.

gene news book Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism. Dowling et al. Nat Chem Biol. 2013 Dec

These crystal structures were obtained using codon-optimized gene synthesis of the QueE gene.GenScript has the expertise to rapidly synthesize codon-optimized gene constructs for the efficient expression of proteins you need for crystallography.

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Transgenic Monkeys Created using CRISPR

monkey gene editing As reported in Nature, scientists have generated the first monkeys harboring specific mutations, through the use of CRISPR-mediated gene editing.

This breakthrough promises to produce better models for studying human disease. CRISPR/Cas9 technology for precise gene editing has already proven successful in other species including in mice, C. elegans, Xenopus tropicalis, and plants.

Why is CRISPR an important breakthrough for creating transgenic monkeys?

Most traditional methods for gene targeting require the introduction of a transgene cassette via homologous recombination. Recombination occurs rarely, so these methods typically use many individual animals – which is challenging to accomplish with non-human primates…Read More

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Gene library for Genome-Wide TALEN Editing in Human Cells

TALEN, TALE plasmids, human genome editing TALENs aren't just for single-gene targeting anymore: researchers recently created TALEN constructs for 18,740 unique protein-coding human genes. In a pilot test of 124 genes, all TALENS were active and disrupted their target genes at high frequencies.

gene news book A library of TAL effector nucleases spanning the human genome, Kim et al. Nature Biotechnology 2013 Mar; 31 (3); 251-8.

To construct their gene library, these researchers ordered custom gene synthesis from GenScript of TALE plasmids containing all possible combinations of four repeat variable di-residue (RVD) DNA sequence modules. GenScript's Combinatorial Assembly Library service can cost-effectively generate gene libraries for high-throughput genome editing, synthetic biology, and other applications. Read More

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Two new TKIs in the spotlight as potential cancer drugs

TKI cancer, Tyrosine Kinase Inhibitors Tyrosine Kinase Inhibitors (TKIs) have already revolutionized the treatment of cancer. But much remains to be learned about how specific receptor tyrosine kinases (RTKs) contribute to cancer, inflammation, and neuropathic pain and how they can be most effectively targeted to alleviate these diseases. These two recent papers use disease-relevant cellular and animal models to characterize new drug candidates and reveal new secrets of cancer biology:

gene news book Discovery and Preclinical Characterization of Novel Small Molecule TRK and ROS1 Tyrosine Kinase Inhibitors for the Treatment of Cancer and Inflammation. Narayanan et al. Plos One. 2013 Dec; 8 (12); e83380

The RTK inhibitor GTx-186 has a unique kinase profile, with activity against TRK-A/B/C, RET, ROS1, NFKB, AP-1, and ALK, conferring the power to quell cancer cell growth in vitro, tumor growth in vivo, and inflammation in disease-relevant cell-based assays and animal models.

gene news book Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor models. Okomato et al. Cancer Lett. 2013 July.

Lenvatinib, currently in clinical trials cancer therapnny as a known VEGFR2/3 inhibitor, was just shown to have antitumor activity RET gene-fusion tumor models. Most exciting, this study suggests there may be synergy between lenvatinib's distinct roles in suppressing angiogenesis and in slowing transformed cell growth – spurring new research on the fundamental oncogenic mechanisms of commonly-observed RET gene fusions.