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Published April 22, 2013 | Supplemental Material + Accepted Version
Journal Article Open

A Synthetic Gene Drive System for Local, Reversible Modification and Suppression of Insect Populations

Abstract

Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a self-perpetuating method of disease prevention but requires a gene drive mechanism to spread these traits to high frequency. Drive mechanisms requiring that transgenes exceed a threshold frequency in order to spread are attractive because they bring about local but not global replacement, and transgenes can be eliminated through dilution of the population with wild-type individuals and 6]. These features are likely to be important in many social and regulatory contexts. Here we describe the first creation of a synthetic threshold-dependent gene drive system, designated maternal-effect lethal underdominance (UD^(MEL)), in which two maternally expressed toxins, located on separate chromosomes, are each linked with a zygotic antidote able to rescue maternal-effect lethality of the other toxin. We demonstrate threshold-dependent replacement in single- and two-locus configurations in Drosophila. Models suggest that transgene spread can often be limited to local environments. They also show that in a population in which single-locus UDMEL has been carried out, repeated release of wild-type males can result in population suppression, a novel method of genetic population manipulation.

Additional Information

© 2013 Elsevier Ltd. Received: October 10, 2012; Revised: December 18, 2012; Accepted: February 27, 2013; Published: March 28, 2013. This work was supported by grants to B.A.H. from the National Institutes of Health (DP10D003878) and the Weston Havens Foundation and to J.M.M. from the Medical Research Council, UK.

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Accepted Version - nihms462458.pdf

Supplemental Material - mmc1.pdf

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August 19, 2023
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