Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

Adriana Adolfi, Valentino M. Gantz, Nijole Jasinskiene, Hsu-Feng Lee, Kristy Hwang, Gerard Terradas, Emily A. Bulger, Arunachalam Ramaiah, Jared B. Bennett, J. J. Emerson, John M. Marshall, Ethan Bier and Anthony A. James ()
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Adriana Adolfi: University of California
Valentino M. Gantz: Section of Cell and Developmental Biology, University of California, San Diego
Nijole Jasinskiene: University of California
Hsu-Feng Lee: University of California
Kristy Hwang: University of California
Gerard Terradas: Section of Cell and Developmental Biology, University of California, San Diego
Emily A. Bulger: Section of Cell and Developmental Biology, University of California, San Diego
Arunachalam Ramaiah: University of California
Jared B. Bennett: Biophysics Graduate Group, Division of Biological Sciences, College of Letters and Science, University of California
J. J. Emerson: University of California
John M. Marshall: Division of Epidemiology & Biostatistics, School of Public Health, University of California
Ethan Bier: Section of Cell and Developmental Biology, University of California, San Diego
Anthony A. James: University of California

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-19426-0

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