Figure 1 - available via license: Creative Commons Attribution-NonCommercial 4.0 International
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(A) Two mechanisms that homing suppression gene drives use to disrupt genes critical for survival and reproduction: homology-directed repair (HDR; left) and disruption via end joining (EJ; right). In both systems, gRNAs initially target nucleases to a specific genomic locus to induce a double-strand break. If a repair template is provided, HDR leads to insertion of the entire drive construct, including the nuclease, gRNAs, and cargo gene (optional), into the targeted site on the homologous chromosome. Activation of end joining repair, an error prone process, will usually knock-out the gene. EJ repair may thus produce resistance alleles that either conserve or disrupt gene function. Resistance alleles that conserve gene function are problematic as they may prevent the success of future homing drive activity (due to mutations disrupting gRNA target site recognition). (B) Perfect gene drive transmission biases drive allele inheritance in offspring by 100%. Figure from Clark (2023) (CC BY 4.0).
Source publication
Fertility-targeted gene drives have been proposed as an ethical genetic approach for managing wild populations of vertebrate pests for public health and conservation benefit.
This manuscript introduces a framework to identify and evaluate target gene suitability based on biological gene function, gene expression, and results from mouse knockout mod...
