Progress toward zygotic and germline gene drives in mice

Chandran Pfitzner, Melissa A. White, Sandra G. Piltz, Michaela Scherer, Fatwa Adikusuma, James N. Hughes, Paul Q. Thomas*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

CRISPR-based synthetic gene drives have the potential to deliver a more effective and humane method of invasive vertebrate pest control than current strategies. Relatively efficient CRISPR gene drive systems have been developed in insects and yeast but not in mammals. Here, we investigated the efficiency of CRISPR-Cas9-based gene drives in Mus musculus by constructing “split drive” systems where gRNA expression occurs on a separate chromosome to Cas9, which is under the control of either a zygotic (CAG) or germline (Vasa) promoter. While both systems generated double-strand breaks at their intended target site in vivo, no homology-directed repair between chromosomes (“homing”) was detectable. Our data indicate that robust and specific Cas9 expression during meiosis is a critical requirement for the generation of efficient CRISPR-based synthetic gene drives in rodents.
Original languageEnglish
Pages (from-to)388-397
Number of pages10
JournalCRISPR Journal
Volume3
Issue number5
DOIs
Publication statusPublished - Oct 2020
Externally publishedYes

Keywords

  • Gene drive
  • CRISPR
  • Biocontrol

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