Synthetic CRISPR-based gene-drive systems have tremendous potential in public health and agriculture, such as for fighting vector-borne diseases or suppressing crop pest populations. These elements can rapidly spread in a population by breaching the inheritance limit of 50% dictated by Mendel’s law of gene segregation, making them a promising tool for population engineering. However, current technologies lack control over their propagation capacity, and there are important concerns about potential unchecked spreading. Here, we describe a gene-drive system in Drosophila that generates an analog inheritance output that can be tightly and conditionally controlled to between 50% and 100%. This technology uses a modified SpCas9 that responds to a synthetic, orally available small molecule, fine-tuning the inheritance probability. This system opens a new avenue to feasibility studies for spatial and temporal control of gene drives using small molecules.

基于CRISPR的合成基因驱动系统在公共卫生和农业领域具有巨大潜力，例如与媒介传播的疾病作斗争或抑制农作物有害生物种群。这些元素可以突破孟德尔基因分离定律规定的50％的遗传限制，从而迅速在人群中传播，使其成为进行人口工程学的有前途的工具。然而，当前的技术缺乏对其传播能力的控制，并且对于潜在的不受限制的传播存在重要的担忧。在这里，我们描述了果蝇中的一个基因驱动系统，该系统生成一个模拟继承输出，可以将其严格地和有条件地控制在50％和100％之间。该技术使用改良的Sp对合成的，口服的小分子有反应的Cas9，可微调遗传概率。该系统为使用小分子进行基因驱动的时空控制开辟了新的途径。