Computational and experimental performance of CRISPR homing gene drive strategies with multiplexed gRNAs.

ABSTRACT: The rapid evolution of resistance alleles poses a major obstacle for genetic manipulation of populations with CRISPR homing gene drives. One proposed solution is using multiple guide RNAs (gRNAs), allowing a drive to function even if some resistant target sites are present. Here, we develop a model of homing mechanisms parameterized by experimental studies. Our model incorporates several factors affecting drives with multiple gRNAs, including timing of cleavage, reduction in homology-directed repair efficiency due to imperfect homology, Cas9 activity saturation, gRNA activity level variance, and incomplete homology-directed repair. We find that homing drives have an optimal number of gRNAs, usually between two and eight, depending on the specific drive type and performance parameters. Thes

SUBMITTER: Champer SE 

PROVIDER: S-EPMC7056305 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature