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2-Locus ​ Cleave and Rescue ​ selfish elements harness a recombination rate-dependent generational clock for self limiting gene drive

Oberhofer, Georg and Ivy, Tobin and Hay, Bruce A. (2020) 2-Locus ​ Cleave and Rescue ​ selfish elements harness a recombination rate-dependent generational clock for self limiting gene drive. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20200710-150639726

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Abstract

Self-limiting gene drive allows control over the spread and fate of linked traits. Cleave and Rescue (ClvR) elements create self-sustaining drive and comprise a DNA sequence-modifying enzyme (Cas9-gRNAs, Cleaver) that disrupts an essential gene, and a tightly linked, uncleavable version of the essential gene (Rescue). ClvR spreads by creating conditions in which those without it die because they lack essential gene function. We show that when ClvR is implemented in a 2-locus format, with key elements - Rescue (and Cargo), and Cas9 and/or gRNAs - located at different genomic positions, spread of the Rescue is self-limiting. Drive strength and duration are determined by a recombination rate-dependent generational clock, providing an important point of control for different ecological and regulatory contexts. We implement 2-locus ClvR in Drosophila. Rescue spreads to high frequency in a Cas9-dependent manner, while the frequency of Cas9 decreases, demonstrating transient drive and loss of future drive potential.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.07.09.196253DOIDiscussion Paper
ORCID:
AuthorORCID
Oberhofer, Georg0000-0003-0930-1996
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 4.0 International license. Posted July 09, 2020. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. This work was carried out with support to B.A.H. from the US Department of Agriculture, National Institute of Food and Agriculture specialty crop initiative under USDA NIFA Award No. 2012-51181-20086, and Caltech. G.O. was supported by a Baxter Foundation Endowed Senior Postdoctoral Fellowship. 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., T.I. and B.A.H.; Modeling, T.I.; 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). Data and materials availability: All data is available in the main text and the supplementary materials. Fly stocks generated in this study are available on request.
Funders:
Funding AgencyGrant Number
NIHP40OD018537
Department of Agriculture2012-51181-20086
CaltechUNSPECIFIED
Donald E. and Delia B. Baxter FoundationUNSPECIFIED
NIH Predoctoral Fellowship5T32GM007616-39
Record Number:CaltechAUTHORS:20200710-150639726
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200710-150639726
Official Citation:2-Locus ​ Cleave and Rescue ​ selfish elements harness a recombination rate-dependent generational clock for self limiting gene drive. Georg Oberhofer, Tobin Ivy, Bruce Hay. bioRxiv 2020.07.09.196253; doi: https://doi.org/10.1101/2020.07.09.196253
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104337
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:10 Jul 2020 22:28
Last Modified:10 Jul 2020 22:28

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