A confinable home and rescue gene drive for population modification

  1. Nikolay P Kandul
  2. Junru Liu
  3. Jared B Bennett
  4. John M Marshall
  5. Omar S Akbari  Is a corresponding author
  1. University of California, San Diego, United States
  2. University of California, Berkeley, United States

Abstract

Homing based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes throughout populations. However, invasion of such drives can be hindered by the accumulation of resistant alleles. To limit this obstacle, we engineer a confinable population modification Home-and-Rescue (HomeR) drive in Drosophila targeting an essential gene. In our experiments, resistant alleles that disrupt the target gene function were recessive lethal, and therefore disadvantaged. We demonstrate that HomeR can achieve an increase in frequency in population cage experiments, but that fitness costs due to the Cas9 insertion limit drive efficacy. Finally, we conduct mathematical modeling comparing HomeR to contemporary gene drive architectures for population modification over wide ranges of fitness costs, transmission rates, and release regimens. HomeR could potentially be adapted to other species, as a means for safe, confinable, modification of wild populations.

Data availability

All data are represented fully within the tables and figures. The gRNA#1PolG2, gRNA#2PolG2, HomeRPolG2, HomeR(B)PolG2, exuL-Cas9, Rcd1r-Cas9, and βTub-Cas9 plasmids and corresponding fly lines are deposited at Addgene.org (159671-159677) and the Bloomington Drosophila Stock Center (91375-91378), respectively.

Article and author information

Author details

  1. Nikolay P Kandul

    Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, United States
    Competing interests
    Nikolay P Kandul, is a consultant for Agragene..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7347-5558
  2. Junru Liu

    Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  3. Jared B Bennett

    Department of Biophysics, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4718-257X
  4. John M Marshall

    Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0603-7341
  5. Omar S Akbari

    Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, United States
    For correspondence
    oakbari@ucsd.edu
    Competing interests
    Omar S Akbari, is a founder of Agragene, Inc., has an equity interest, and serves on the company's Scientific Advisory Board..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6853-9884

Funding

Defense Advanced Research Projects Agency (HR0011-17-2-0047)

  • Omar S Akbari

National Institutes of Health (R21RAI149161A)

  • Omar S Akbari

National Institutes of Health (R01AI151004)

  • Omar S Akbari

National Institutes of Health (DP2AI152071)

  • Omar S Akbari

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Claude Desplan, New York University, United States

Publication history

  1. Received: December 19, 2020
  2. Accepted: March 4, 2021
  3. Accepted Manuscript published: March 5, 2021 (version 1)
  4. Version of Record published: March 17, 2021 (version 2)

Copyright

© 2021, Kandul et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Nikolay P Kandul
  2. Junru Liu
  3. Jared B Bennett
  4. John M Marshall
  5. Omar S Akbari
(2021)
A confinable home and rescue gene drive for population modification
eLife 10:e65939.
https://doi.org/10.7554/eLife.65939

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