Center for Bioinformatics, Center for Life Sciences, School of Life Sciences, Peking University, Beijing, China.
Mol Ecol. 2024 Oct;33(19):e17530. doi: 10.1111/mec.17530. Epub 2024 Sep 16.
Gene drives have great potential for suppression of pest populations and removal of exotic invasive species. CRISPR homing suppression drive is a powerful but unconfined drive, posing risks of uncontrolled spread. Thus, developing methods for confining a gene drive is of great significance. Tethered drive combines a confined system such as Toxin-Antidote Recessive Embryo drive with a strong drive such as a homing suppression drive. It can prevent the homing drive from spreading beyond the confined drive and can be constructed readily, giving it good prospects for future development. However, we have found that care must be taken when deploying tethered drive systems in some scenarios. Simulations of tethered drive in a panmictic population model reveal that successful deployment requires a proper release ratio between the two components, tailored to prevent the suppression drive from eliminating the confined system before it has the chance to spread. Spatial models where the population moves over a one-dimensional landscape display a more serious phenomenon of drive wave interference between the two tethered drive components. If the faster suppression drive wave catches up to the confined drive wave, success is still possible, but it is dependent on drive performance and ecological parameters. Two-dimensional simulations further restrict the parameter range for drive success. Thus, careful consideration must be given to drive performance and ecological conditions, as well as specific release proposals for potential application of tethered drive systems.
基因驱动具有抑制害虫种群和消除外来入侵物种的巨大潜力。CRISPR 归巢抑制驱动是一种强大但不受控制的驱动，存在不可控传播的风险。因此，开发限制基因驱动的方法具有重要意义。系绳驱动将受限系统（如毒素-解毒隐性胚胎驱动）与强驱动（如归巢抑制驱动）结合在一起。它可以防止归巢驱动传播超出受限驱动的范围，并且易于构建，因此具有很好的发展前景。然而，我们发现，在某些情况下，在部署系绳驱动系统时必须小心谨慎。在均匀混合种群模型中的系绳驱动模拟表明，成功部署需要两个组件之间适当的释放比例，以防止抑制驱动在有机会传播之前消灭受限系统。在种群在一维景观上移动的空间模型中，两个系绳驱动组件之间的驱动波干扰现象更为严重。如果更快的抑制驱动波赶上受限驱动波，仍然有可能成功，但这取决于驱动性能和生态参数。二维模拟进一步限制了驱动成功的参数范围。因此，必须仔细考虑驱动性能和生态条件，以及潜在应用系绳驱动系统的具体释放方案。
