Genetic Engineering & Biotechnology News

SEP15 2017

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Genetic Engineering & Biotechnology News | GENengnews.com | SEPTEMBER 15, 2017 | 15 cautions Dr. Bier. A more desirable alterna- tive involves modifying attributes that are undesirable, such as an organism's ability to propagate disease or its preference for one type of crop versus another. "One can ob- tain more of an effect by just changing that characteristic and not trying to kill the or- ganism," advises Dr. Bier. In introducing genetic modifications into mosquitoes, Dr. Bier and colleagues exten- sively rely on the ability to generate effector molecules that bind to parasites and render them unable to transfer to the body of the mosquito. One of the key requirements of these molecules is their ability to bind with high affinity to epitopes on the parasite. "Technologies that we would value for this work include rapid protein evolution binders, which are molecules that are ca- pable of binding random input peptides," maintains Dr. Bier. After peptides are pro- vided, genetically encodable binders that interact with them could be used in vivo to tether them to components in the mosquito to either kill the parasites or make them ag- gregate. "[Using] evolutionary synthetic biology approaches to make novel protein- interacting peptides," adds Dr. Bier, "would be extremely valuable for our work." Sterilizing Populations "We look at gene drive as something that can bias inheritance and is differentially in- cluded in the offspring, and that can be cou- pled to a trait that might be of use in terms of controlling the mosquito population," says Tony Nolan, Ph.D., senior research fellow at Imperial College London. In a recent study, Dr. Nolan and colleagues designed a CRIS- PR/Cas9-based approach to individually target and disrupt three Anopheles gambiae genes that have high ovarian expression and tissue specificity. "We disrupted key fertility genes," in- forms Dr. Nolan. "That allowed us to intro- duce an element that can cause population reduction, which is viewed as the most suc- cessful strategy today to control malaria." For two of these loci, the constructs were predicted to disappear from the population over time, but for the third one, the gene dis- ruption met the minimum requirements for targeting female reproduction by gene drive in a mosquito population. One of the challenges related to the imple- mentation of gene drives is intimately related to the emergence of resistance. "Anything that tries to suppress a population would impose a selection pressure on the population," states Dr. Nolan. An advantage, when using gene drives, is that some of the resistance mecha- nisms are foreseeable. "Therefore, one can plan in advance and make the emergence of resistance much less likely," asserts Dr. Nolan. Another challenge is the need to demon- strate that gene-drive technology, which is still new, can be trusted. Large amounts of data are needed to confirm that gene drive works and is safe. "There is a lot of testing that should happen between building some- thing in the laboratory and making some- thing the field," advises Dr. Nolan. "This is going to be a very long process." Comparing Alternative Strategies "We think of gene drives as having three categories of challenges or issues," says Aus- tin Burt, Ph.D., professor of evolutionary genetics at Imperial College London. The challenges, Dr. Burt suggests, are techno- logical (the ability to "generate constructs that do what we want them to do"); regu- latory (the ability to "obtain permission to use the technology that we develop"); and in a sense, communal (the ability to "broaden stakeholder acceptance in terms of people wanting to have this technology"). Almost 15 years ago, Dr. Burt was the first investigator to propose the use of gene drives based on homing endonuclease genes. Homing endonuclease genes encode highly specific endonucleases with recognition se- quences that occur only once in a genome and can activate recombination repair sys- tems by inducing double-stranded chromo- somal breaks in the homologous chromo- some. As a result of the homology-directed repair process, the endonuclease gene is cop- ied to the broken chromosome. This process can be used to spread the gene through a population. Flawless Quantify Protein Impurities with Enzo's Bioprocess Detection Kits Ultrasensitive | Broad Range | High Specifi city Optimize and Monitor Product Integrity with Ultrasensitive Solutions Contamination monitoring is critical in bioprocessing. Protein contamination can decrease the effi cacy of a biologic and increase its immunogenicity. Early detection of contaminants mitigates risks and reduces cost. 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