One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a Cas9 nuclease that is constitutively active, impeding our control over their propagation abilities and limiting the generation of alternative gene drive arrangements. Yet, other nucleases such as the temperature sensitive Cas12a have not been explored for gene drive designs in insects. To address this, we herein present a proof-of-concept gene-drive system driven by Cas12a that can be regulated via temperature modulation. Furthermore, we combined Cas9 and Cas12a to build double gene drives capable of simultaneously spreading two independent engineered alleles. The development of Cas12a-mediated gene drives provides an innovative option for designing next-generation vector control strategies to combat disease vectors and agricultural pests.

减少媒介传播疾病影响的一种方法是使用基于 CRISPR 的基因驱动，这种基因驱动能够操纵昆虫种群，因为它们能够将所需的遗传性状快速传播到目标种群中。然而，目前所有的基因驱动都采用具有组成型活性的 Cas9 核酸酶，这阻碍了我们对其传播能力的控制，并限制了替代基因驱动排列的产生。然而，其他核酸酶（例如温度敏感的 Cas12a）尚未被探索用于昆虫的基因驱动设计。为了解决这个问题，我们在此提出了一种由 Cas12a 驱动的概念验证基因驱动系统，该系统可以通过温度调节进行调节。此外，我们结合 Cas9 和 Cas12a 构建了双基因驱动器，能够同时传播两个独立的工程等位基因。Cas12a介导的基因驱动的发展为设计下一代病媒控制策略以对抗病媒和农业害虫提供了创新选择。