Department of Microbiology & Molecular Genetics, University of California, Irvine, CA, 92697-3900, USA.
Liverpool School of Tropical Medicine, Vector Biology Department, L3 5QA, Liverpool, UK.
Nat Commun. 2020 Nov 3;11(1):5553. doi: 10.1038/s41467-020-19426-0.
Cas9/gRNA-mediated gene-drive systems have advanced development of genetic technologies for controlling vector-borne pathogen transmission. These technologies include population suppression approaches, genetic analogs of insecticidal techniques that reduce the number of insect vectors, and population modification (replacement/alteration) approaches, which interfere with competence to transmit pathogens. Here, we develop a recoded gene-drive rescue system for population modification of the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and rare functional resistant alleles do not prevent drive invasion. Small cage trials show that single releases of gene-drive males robustly result in efficient population modification with ≥95% of mosquitoes carrying the drive within 5-11 generations over a range of initial release ratios.
Cas9/gRNA 介导的基因驱动系统为控制媒介传播病原体的遗传技术的发展提供了帮助。这些技术包括种群抑制方法、减少昆虫媒介数量的基因杀虫技术的遗传类似物,以及种群修饰(替代/改变)方法,这些方法干扰了病原体传播的能力。在这里,我们开发了一种针对疟疾传播媒介按蚊的经重编码的基因驱动挽救系统,该系统通过恢复其功能来减轻驱动基因整合到犬尿氨酸羟化酶基因中对雌性造成的负担。非功能性抗性等位基因通过显性的母性效应与较慢的标准负选择相结合而被消除,而罕见的功能性抗性等位基因不会阻止驱动入侵。小型笼试验表明,单次释放基因驱动的雄性可以在 5-11 代内迅速有效地进行种群修饰,在一系列初始释放比例下,有≥95%的蚊子携带驱动基因。