Gene drive systems have long been sought to modify mosquito populations and thus combat malaria and dengue. Powerful gene drive systems have been developed in laboratory experiments, but may never be used in practice unless they can be shown to be acceptable through rigorous field-based testing. Such testing is complicated by the anticipated difficulty in removing gene drive transgenes from nature. Here, we consider the inclusion of self-elimination mechanisms into the design of homing-based gene drive transgenes. This approach not only caused the excision of the gene drive transgene, but also generates a transgene-free allele resistant to further action by the gene drive. Strikingly, our models suggest that this mechanism, acting at a modest rate (10%) as part of a single-component system, would be sufficient to cause the rapid reversion of even the most robust homing-based gene drive transgenes, without the need for further remediation. Modelling also suggests that unlike gene drive transgenes themselves, self-eliminating transgene approaches are expected to tolerate substantial rates of failure. Thus, self-elimination technology may permit rigorous field-based testing of gene drives by establishing strict time limits on the existence of gene drive transgenes in nature, rendering them essentially biodegradable.

This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'.

长期以来，人们一直在寻求基因驱动系统来改变蚊子的数量，从而对抗疟疾和登革热。强大的基因驱动系统已经在实验室实验中开发出来，但可能永远不会在实践中使用，除非它们可以通过严格的实地测试证明是可以接受的。由于从自然界中去除基因驱动转基因的预期困难，这种测试变得复杂。在这里，我们考虑将自我消除机制纳入基于归巢的基因驱动转基因的设计中。这种方法不仅导致基因驱动转基因的切除，而且产生了一个无转基因等位基因，可以抵抗基因驱动的进一步作用。引人注目的是，我们的模型表明，作为单组分系统的一部分，这种机制以适度的速率 (10%) 起作用，即使是最强大的基于归巢的基因驱动转基因也足以导致快速逆转，而无需进一步修复。建模还表明，与基因驱动转基因本身不同，自我消除转基因方法预计可以容忍大量失败率。因此，自我消除技术可以通过对自然界中基因驱动转基因的存在建立严格的时间限制，使它们基本上可生物降解，从而允许对基因驱动进行严格的现场测试。

本文是主题问题“蚊媒疾病的新型控制策略”的一部分。