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Gene drive that results in addiction to a temperature sensitive version of an essential gene triggers population collapse in Drosophila

Oberhofer, Georg and Ivy, Tobin and Hay, Bruce A. (2021) Gene drive that results in addiction to a temperature sensitive version of an essential gene triggers population collapse in Drosophila. . (Unpublished)

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One strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise benign virus or chemical, or occur naturally on a seasonal basis, such as a change in temperature. Cleave and Rescue (ClvR) selfish genetic elements use Cas9 and gRNAs to disrupt endogenous versions of an essential gene, while also including a Rescue version of the essential gene resistant to disruption. ClvR spreads by creating loss-of-function alleles of the essential gene that select against those lacking it, resulting in populations in which the Rescue provides the only source of essential gene function. In consequence, if function of the Rescue, a kind of Trojan horse now omnipresent in a population, is condition-dependent, so too will be the survival of that population. To test this idea we created a ClvR in Drosophila in which Rescue activity of an essential gene, dribble, requires splicing of a temperature-sensitive intein (TS-ClvR^(dbe)). This element spreads to transgene fixation at 23°C, but when populations now dependent on Ts-ClvR^(dbe) are shifted to 29°C death and sterility result in a rapid population crash. These results show that conditional population elimination can be achieved. A similar logic, in which Rescue activity is conditional, could also be used in HEG-based drive, and to bring about suppression and/or killing of specific individuals in response to other stimuli.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Oberhofer, Georg0000-0003-0930-1996
Ivy, Tobin0000-0002-9116-3854
Hay, Bruce A.0000-0002-5486-0482
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. This version posted July 4, 2021. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. This work was carried out with support to BAH from the US Department of Agriculture, National Institute of Food and Agriculture specialty crop initiative under USDA NIFA Award No. 2012-51181-20086 and the Caltech Resnick Sustainability Institute. G.O. was supported by a Baxter Foundation Endowed Senior Postdoctoral Fellow ship and the Caltech Resnick Sustainability Institute. T.I. was supported by NIH training grant 5T32GM007616-39. Author Contributions: Conceptualization, G.O., T.I. and B.A.H.; Methodology, G.O., T.I. and B.A.H.; Investigation, G.O. and B.A.H.; Writing – Original Draft, G.O. and B.A.H.; Writing – Review & Editing, G.O., T.I. and B.A.H.; Funding Acquisition, G.O. and B.A.H. Competing interests: The authors have filed patent applications on ClvR and related technologies (U.S. Application No. 15/970,728 and No. 16/673,823; provisional patent No. CIT-8511-P). Data availability: All data is available in the main text or the supplementary materials.
Group:Resnick Sustainability Institute
Funding AgencyGrant Number
Department of Agriculture2012-51181-20086
Resnick Sustainability InstituteUNSPECIFIED
Baxter FoundationUNSPECIFIED
NIH Predoctoral Fellowship5T32GM007616-39
Subject Keywords:Gene drive, Drosophila, selfish genetic element, population suppression
Record Number:CaltechAUTHORS:20210712-144929811
Persistent URL:
Official Citation:Gene drive that results in addiction to a temperature sensitive version of an essential gene triggers population collapse in Drosophila. Georg Oberhofer, Tobin Ivy, Bruce A. Hay. bioRxiv 2021.07.03.451005; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109774
Deposited By: Tony Diaz
Deposited On:12 Jul 2021 15:04
Last Modified:12 Jul 2021 15:04

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