Chemical Controllable Gene Drive in Drosophila

ACS Synth Biol. 2020 Sep 18;9(9):2362-2377. doi: 10.1021/acssynbio.0c00117. Epub 2020 Aug 24.

Abstract

Gene drive systems that propagate transgenes via super-Mendelian inheritance can potentially control insect-borne diseases and agricultural pests. However, concerns have been raised regarding unforeseen ecological consequences, and methods that prevent undesirable gene drive effects have been proposed. Here, we report a chemical-induced control of gene drive. We prepared a CRISPR-based gene drive system that can be removed by a site-specific recombinase, Rippase, the expression of which is induced by the chemical RU486 in fruit flies. Exposure of fruit flies to RU486 resulted in 7-12% removal of gene drive elements at each generation, leading to a significant reduction in gene drive-fly propagation. Mathematical modeling and simulation suggest that our system offers several advantages over a previously reported gene drive control system. Our chemical control system can provide a proof-of-principle for the reversible control of gene drive effects depending on ecological status and human needs.

Keywords: CRISPR-Cas9 system; Rippase; gene drive; mutagenic chain reaction; population genetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • CRISPR-Cas Systems / genetics
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Female
  • Gene Drive Technology / methods*
  • Gene Expression Regulation / drug effects*
  • Male
  • Mifepristone / pharmacology*
  • Models, Genetic
  • RNA, Guide, CRISPR-Cas Systems / metabolism
  • Recombinases / genetics
  • Recombinases / metabolism

Substances

  • RNA, Guide, CRISPR-Cas Systems
  • Recombinases
  • Mifepristone