National Academies Hit the Brakes on Gene Drive-Modified Organisms.


Despite their potential for fighting Zika,malaria,andotherpublichealth scourges,organismsthathavebeen engineered to quickly spread genetic modifications through a population—and possibly an entire species—are not ready for release into the wild, a committee of interdisciplinary experts concluded in a recent report by the National Academies of Sciences, Engineering, and Medicine ( So-called gene drive–modified organisms “require more research in laboratoriesandhighlycontrolled fieldtrials,” thecommitteesaid inastatement ( Gene drives are systems of “biased inheritance” that enhance a genetic element’s ability to pass fromparent organism to offspring through sexual reproduction. These selfish genetic elements could be genesor their fragments, all orpartsof chromosomes, or noncoding DNA, the report stated. “You’re looking at the passage of a trait throughapopulation at a greater than50% frequency,which is [higher than]whatMendelian genetics would give you,” explained committeemember Lisa Taneyhill, PhD, associate professor in the department of animal and avian sciences at the University of Maryland, College Park. What’s in a Gene Drive? Gene drives occur naturally in many species, but in the past few years the emergence of highly efficient gene-editing tools hasopenedthe field tohumantinkering.Researchers described the use of CRISPRCas9 to create the first gene drive–modifiedorganism—yeast—early lastyear (DiCarlo JE et al. Nat Biotechnol. 2015;33[12]:12501255). Gene drive–modified fruit flies and mosquitoes have followed (Gantz VM et al. Science. 2015;348[6233]:442-444; Gantz VM et al. Proc Natl Acad Sci U S A. 2015; 112[49]:E6736-E6743; Hammond A et al. Nat Biotechnol. 2016;34[1]:78-83). Unlike traditional genetic modifications,genedrivesaredesignedtospreadand persist from one generation to the next, theoretically leading to “fixation,” where changes are present in 99% ormore of the organisms in a population. KevinEsvelt,PhD,nowassistantprofessor and leader of the sculpting evolution group at the MIT Media Laboratory, was on theHarvardteamthatdevelopedgenedrive– modified yeast and safeguards for their use. Inaninterview,hedescribedCRISPRasapencil for rewriting DNA code.With it, scientists erase theoriginal codeandwrite inanewsequence. Building on the use of CRISPR, the gene drive goes a step further. “With a gene drive, you write in the sequence that youwant, and you alsowrite in the instructions for making the pencil, so then the organism knows how tomake the pencil and do the edits... on its own,” Esvelt said. Given enough generations, he said, “Eventually you have erased and rewritten every copy present in the wild population, if you do it right.” Genedrives can reduce apopulation or change its genotype. The technology is not practical in species with long generation times, includinghumans,but itcouldbeused to conserve threatenedor endangered species, combat invasive species, or control agriculturalpests. It isparticularly tantalizingas apotentialweaponagainst vector-borne infectious disease. Genetically modified Aedes aegypti mosquitoes with a self-limiting gene that shortens the life of their offspring, preventing them from reproducing, have already beendeployed to reducedengue andother diseases ina fewprojectsoutside theUnited States.However, theydonotpossessagene drive, and theymustbeperiodically reintroduced into the environment because the modification doesn’t persist in the population. In contrast, a single gene drive– modified mosquito engineered to resist a pathogen could, in a relatively short time,

DOI: 10.1001/jama.2016.8830

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@article{Abbasi2016NationalAH, title={National Academies Hit the Brakes on Gene Drive-Modified Organisms.}, author={Jennifer Abbasi}, journal={JAMA}, year={2016}, volume={316 5}, pages={482-3} }