Homing gene drive strains for genetic suppression of agricultural insect pests

Homing gene drive strains for genetic suppression of agricultural insect pests

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Yadav, Amarish K.; Tarrand, Ariel E.; Scott, Maxwell J.,  Entomologia Generalis,  45:1577 - 1590. 2025.

Agricultural insect pests cause substantial losses in crop productivity each year. Genetic-based strategies provide economical and environmentally friendly ways to limit pests that reproduce sexually. In contrast to conventional genetic methods (e.g. SIT), homing gene drives (HGDs) are potentially capable of suppressing or modifying an entire pest population in a short period of time after releasing a small number of HGD insects. The advent of CRISPR/Cas gene editing tools has simplified the engineering of gene drives, and the progress made on HGDs in various insects in the recent past is encouraging. However, to date HGDs have been developed and evaluated in only a few agricultural pest species. These drives have been designed to suppress populations by targeting genes essential for female development or fertility. Homing gene drive relies on homology directed repair (HDR) of the Cas9-mediated double-stranded DNA break in germ cells. Consequently, the use of other DNA repair pathways such as non-homologous end joining (NHEJ) and micro-homology mediated end joining (MMEJ) can retard homing. Further, establishment of functional resistant alleles through these end-joining pathways is one of the major challenges associated with HGDs. Development of HGDs in some pest species is challenging due to the technical difficulties of making transgenics. Identification and characterization of germline-specific promoters and other regulatory elements to achieve precise HDR (in early meiosis) can facilitate efficient homing. In this review, we highlight the recent progress made towards developing HGDs in agricultural insect pests with insights gained from studies in model organisms (e.g. Drosophila melanogaster).