Journal
ACS SYNTHETIC BIOLOGY
Volume 9, Issue 9, Pages 2362-2377Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.0c00117
Keywords
gene drive; mutagenic chain reaction; CRISPR-Cas9 system; population genetics; Rippase
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Funding
- National Research Foundation of Korea (NRF) Grant [NRF-2016R1A5A2008630, NRF-2017R1A2B3004198, NRF-2017M3A9B4062403]
- Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea - Korean Government (MSIP) [HI17C0676]
- Yonsei University New Faculty Research Seed Money Grant of 2015
- Yonsei University College of Medicine [6-2015-0086]
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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.
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