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Esvelt, K. M.

Publications and source records attributed to Esvelt, K. M..

2 recordsLinked to original sources

Current CRISPR gene drive systems are likely to be highly invasive in wild populations

Recent reports have suggested that CRISPR-based gene drives are unlikely to invade wild populations due to drive-resistant alleles that prevent cutting. Here we develop mathematical models based on existing empirical data to explicitly test this assumption. We show that although resistance prevents drive systems from spreading to fixation in large populations, even the least effective systems reported to date are highly invasive. Releasing a small number of organisms often causes invasion of the local population, followed by invasion of additional populations connected by very low gene flow rates. Examining the effects of mitigating factors including standing variation, inbreeding, and family size revealed that none of these prevent invasion in realistic scenarios. Highly effective drive systems are predicted to be even more invasive. Contrary to the National Academies report on gene drive, our results suggest that standard drive systems should not be developed nor field-tested in regions harboring the host organism.

synthetic biology

Daisyfield gene drive systems harness repeated genomic elements as a generational clock to limit spread

Methods of altering wild populations are most useful when inherently limited to local geographic areas. Here we describe a novel form of gene drive based on the introduction of multiple copies of an engineered daisy sequence into repeated elements of the genome. Each introduced copy encodes guide RNAs that target one or more engineered loci carrying the CRISPR nuclease gene and the desired traits. When organisms encoding a drive system are released into the environment, each generation of mating with wild-type organisms will reduce the average number of the guide RNA elements per daisyfield organism by half, serving as a generational clock. The loci encoding the nuclease and payload will exhibit drive only as long as a single copy remains, placing an inherent limit on the extent of spread.

synthetic biology