Overriding Mendelian Inheritance in Arabidopsis with A CRISPR Toxin–Antidote Gene Drive that Impairs Pollen Germination
    作者: Yang Liu, Bingke Jiao, Jackson Champer & Wenfeng Qian
    刊物名称: Nature Plants
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    摘要:
    Synthetic gene drives, inspired by natural selfish genetic elements and transmitted to progeny at super-Mendelian (>50%) frequencies, present transformative potential for disseminating traits that benefit humans throughout wild populations, even facing potential fitness costs. Here we constructed a gene drive system in plants called CRISPR-Assisted Inheritance utilizing NPG1 (CAIN), which uses a toxin–antidote mechanism in the male germline to override Mendelian inheritance. Specifically, a guide RNA–Cas9 cassette targets the essential No Pollen Germination 1 (NPG1) gene, serving as the toxin to block pollen germination. A recoded, CRISPR-resistant copy of NPG1 serves as the antidote, providing rescue only in pollen cells that carry the drive. To limit potential consequences of inadvertent release, we used self-pollinating Arabidopsis thaliana as a model. The drive demonstrated a robust 88–99% transmission rate over two successive generations, producing minimal resistance alleles that are unlikely to inhibit drive spread. Our study provides a strong basis for rapid genetic modification or suppression of outcrossing plant populations.