CRISPR-based homing gene drive is a genetic control technique aiming to modify or eradicate natural populations. This technique is based on the release of individuals carrying an engineered piece of DNA that can be preferentially inherited by the progeny. The development of countermeasures is important to control the spread of gene drives, should they result in unanticipated damages. One proposed countermeasure is the introduction of individuals carrying a brake construct that targets and inactivates the drive allele but leaves the wild-type allele unaffected. Here we develop models to investigate the efficiency of such brakes. We consider a variable population size and use a combination of analytical and numerical methods to determine the conditions where a brake can prevent the extinction of a population targeted by an eradication drive. We find that a brake is not guaranteed to prevent eradication and that characteristics of both the brake and the drive affect the likelihood of recovering the wild-type population. In particular, brakes that restore fitness are more efficient than brakes that do not. Our model also indicates that threshold-dependent drives (drives that can spread only when introduced above a threshold) are more amenable to control with a brake than drives that can spread from an arbitrary low introduction frequency (threshold-independent drives). Based on our results, we provide practical recommendations and discuss safety issues.

基于 CRISPR 的归巢基因驱动是一种旨在改变或根除自然种群的基因控制技术。这项技术的基础是释放携带经过改造的 DNA 片段的个体，该 DNA 片段可以优先由后代遗传。如果基因驱动造成意外损害，制定对策对于控制基因驱动的传播非常重要。一项提出的对策是引入携带制动结构的个体，该制动结构靶向并灭活驱动等位基因，但使野生型等位基因不受影响。在这里，我们开发模型来研究此类制动器的效率。我们考虑可变的种群规模，并结合分析和数值方法来确定刹车可以防止根除运动所针对的种群灭绝的条件。我们发现制动不能保证防止根除，制动和驱动的特性都会影响恢复野生型种群的可能性。特别是，恢复健康的刹车比不恢复健康的刹车更有效。我们的模型还表明，与可以从任意低引入频率开始传播的驱动器（与阈值无关的驱动器）相比，与阈值相关的驱动器（仅在高于阈值时才可以传播的驱动器）更适合用制动器控制。根据我们的结果，我们提供实用的建议并讨论安全问题。