Department of Cell and Developmental Biology, University of California San Diego, San Diego, CA, USA.
Tata Institute for Genetics and Society, University of California San Diego, San Diego, CA, USA.
Nat Commun. 2024 Nov 17;15(1):9961. doi: 10.1038/s41467-024-54210-4.
Insecticide resistance (IR) poses a significant global challenge to public health and welfare. Here, we develop a locally-acting unitary self-eliminating allelic-drive system, inserted into the Drosophila melanogaster yellow (y) locus. The drive cassette encodes both Cas9 and a single gRNA to bias inheritance of the favored wild-type (1014 L) allele over the IR (1014 F) variant of the voltage-gated sodium ion channel (vgsc) target locus. When enduring a fitness cost, this transiently-acting drive can increase the frequency of the wild-type allele to 100%, depending on its seeding ratio, before being eliminated from the population. However, in a fitness-neutral "hover" mode, the drive maintains a constant frequency in the population, completely converting IR alleles to wild-type, even at low initial seeding ratios.
杀虫剂抗性（IR）对公共卫生和福利构成了重大的全球性挑战。在这里，我们开发了一种局部作用的单一自我消除等位基因驱动系统，插入黑腹果蝇的黄色（y）基因座。该驱动盒编码 Cas9 和单个 gRNA，以偏向于电压门控钠离子通道（vgsc）靶基因座中有利的野生型（1014L）等位基因的遗传，而不是对 IR（1014F）变体的遗传。当承受适应度成本时，这种瞬时作用的驱动可以根据其播种比将野生型等位基因的频率提高到 100%，然后从种群中消除。然而，在适应度中性的“悬停”模式下，驱动在种群中保持恒定的频率，即使在低初始播种比下，也能将 IR 等位基因完全转化为野生型。
