Behavior of homing endonuclease gene drives targeting genes required for viability or female fertility with multiplexed guide RNAs

• DOI: 10.1073/pnas.1805278115
• Publication Date: 2018-09-17T19:16:48Z
• Authors: Georg Oberhofer; Tobin Ivy; Bruce A. Hay
• Keywords: Homing endonuclease; Gene drive; Homing (biology)

Significance Homing endonuclease gene (HEG)-based drive can bring about population suppression when genes required for viability or fertility are targeted. However, these strategies vulnerable to failure through mechanisms that create alleles resistant cleavage but retain wild-type function. We show resistance allele creation be prevented the use of guide RNAs designed cleave a at four target sites. homing rates were modest, and HEGs unstable during homing. In addition, promoter active in female germline resulted levels HEG carryover compromised HEG-bearing heterozygotes, thereby preventing drive. propose help overcome problems next-generation systems.