Genetic Engineering & Biotechnology News

SEP15 2017

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16 | SEPTEMBER 15, 2017 | GENengnews.com | Genetic Engineering & Biotechnology News In a recent modeling analysis, Dr. Burt and colleagues evaluated three different strategies—population suppression through dual-germline fertility disruption, population suppression with a driving-Y chromosome, and mosquito population replacement—to predict how each strategy would perform in a real-life setting from sub-Saharan Africa. Each strategy, despite presenting a unique set of challenges, was highly effective at reduc- ing malaria transmission. "The point of this work is to help de- fine what it is that would constitute techni- cal success," declares Dr. Burt. A broader understanding of success, he adds, would encompass the gene-drive attributes that "need to be in place to predict the successful transition of the work from the laboratory to the field." Gene Drive in Practice Many different techniques have been de- veloped, and many more could be developed, to incorporate gene drives, says Zach N. Adel- man, Ph.D., associate professor of entomol- ogy at Texas A&M University. What these techniques have in common, he suggests, is the need to address the issue of specificity. The blessing of specificity is that off-target effects are minimized with a highly specific nuclease. The curse of specificity is that when sequence variation is pronounced in a natu- ral population, or when new changes arise, a very specific nuclease will lack or come to lose the ability to recognize the genomic re- gion that needs to be targeted. "This is what investigators have come up against recently," insists Dr. Adelman. Even though sequence variations may naturally occur at low levels in a population, such variations could quickly become more prevalent if a gene drive were to bring with it any kind of fitness cost. "We are trying to develop nucleases that are so specific that they do not cause undesirable changes, but are not so specific that it takes only a single change, one that might already occur in na- ture, to make them nonfunctional," explains Dr. Adelman. Dr. Adelman and colleagues recently pro- posed a two-step approach for gene editing in organisms that are difficult to manipulate genetically, such as mosquitoes. In this ap- proach, the first step is to evaluate candidate site-specific nucleases. (Many synthetic guide RNA molecules are initially examined in vivo.) The second step is to carry out germ- line-based editing while constraining the choice of DNA repair response. (RNA in- terference is used to suppress components of the nonhomologous end-joining response.) Suppression of the Ku70 component sub- stantially improved the rates of homology- directed repair and resulted in gene insertion frequencies of around 2–3%. "The regulatory agencies are still coming to grips with what it means to have a tech- nology that will be used in an environment that is beyond a containment barrier," says Dr. Adelman. In the case of previous initia- tives to generate genetically engineered prod- ucts, such as salmon and crops, these were confined to a contained environment, did not move beyond where they were breeded (salmon) or planted (crops), and did not ad- mix intentionally with wild population. "But the goal in gene drive is to admix, and we are still working out the pathways," declares Dr. Adelman. The pathways from the laboratory to the field will have to be constructed de novo at the same time that the regulatory frameworks are constructed, he suggests. Gene Drives Continued from page 15 OMICS Insights Genomics & Proteomics Two leaders in developing innovative epigenetic tools, NuGEN Technologies and Cambridge Epigenetix (CEGX), recently announced that they have entered into a strategic partnership agreement to integrate the CEGX TrueMethyl technology for oxidative bisulfite sequencing (oxBS-Seq) with NuGEN's innovative NGS library preparation kits. The signing of the agreement will enable CEGX to focus on its epigenetic biomarker discovery programs, both in-house and in partnership with leading biopharma companies, and will further strengthen NuGEN's epigenetics portfolio of whole- genome Methyl-Seq, reduced representation bisulfite sequencing (RRBS), and patented SPET target enrich- ment systems. "This partnership will enable both CEGX and NuGEN to leverage our strengths to facilitate advances in the epigenetics field," remarked Jason Mellad, Ph.D., CEO at Cambridge Epigenetix, in a press release. "CEGX is com- mitted to realizing the promise of epigenetics through the development of improved, minimally invasive diagnostic and prognostic tests for accurate and early detection of a range of diseases, including cancer. Nu- GEN's reach and reputation for delivering high-quality genomics solutions to the market make them the ideal partner to further develop TrueMethyl technology to deliver a range of new products to enhance epi- genetics research." The epigenetic DNA modifications 5-hydroxymethyl- cytosine (5hmC) and 5-methylcytosine (5mC) play very different roles in gene regulation. Cambridge Epigenetix enhanced the appreciation of 5hmC through the intro- duction of its TrueMethyl oxBS-Seq system. Their devel- opments have enabled researchers to further elucidate the role of DNA methylation in disease occurrence and progression, highlighting the potential for such epigen- etic marks in the development of improved diagnostic and prognostic assays. The integration of TrueMethyl oxBS and NuGEN's patented library preparation tech- nologies will broaden the scope of accessible samples for the detection of these emerging markers. "We are delighted to be working with CEGX to provide the tools to improve the understanding and appreciation of epigenetics in cellular function," stated Nitin Sood, Ph.D., CEO of NuGEN Technologies. "By combining the TrueMethyl oxBS technology with our NGS library preparation kits, we will provide our customers with whole genome and targeted methylation products to unlock the tremendous potential of epigenetics. The technology complements our Methyl-Seq and single primer enrichment technology product lines, and we are delighted to provide researchers with the most comprehensive solution for epigenetics research." n New Partnership Set to Enhance Epigenetics Research Efforts Discover what's new from the leading journal on post-genomic medicine and integrative biology liebertpub.com/omi Sign Up for TOC Alerts Discover what's new from the leading journal on post-genomic medicine and integrative biology liebertpub.com/omi Sign Up for TOC Alerts Editor-in-Chief: Vural Özdemir, MD, PhD, DABCP

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