Department of Life Sciences, Imperial College London, London, United Kingdom.
Elife. 2021 Apr 13;10:e58791. doi: 10.7554/eLife.58791.
Gene drives for mosquito population replacement are promising tools for malaria control. However, there is currently no clear pathway for safely testing such tools in endemic countries. The lack of well-characterized promoters for infection-relevant tissues and regulatory hurdles are further obstacles for their design and use. Here we explore how minimal genetic modifications of endogenous mosquito genes can convert them directly into non-autonomous gene drives without disrupting their expression. We co-opted the native regulatory sequences of three midgut-specific loci of the malaria vector to host a prototypical antimalarial molecule and guide-RNAs encoded within artificial introns that support efficient gene drive. We assess the propensity of these modifications to interfere with the development of and their effect on fitness. Because of their inherent simplicity and passive mode of drive such traits could form part of an acceptable testing pathway of gene drives for malaria eradication.
基因驱动用于蚊群替换是控制疟疾的有前途的工具。然而，目前在流行地区国家中还没有安全测试此类工具的明确途径。缺乏针对感染相关组织的特征明确的启动子以及监管障碍，是其设计和使用的进一步障碍。在这里，我们探讨了如何通过对内在的蚊子基因进行最小的遗传修饰，将其直接转化为非自主基因驱动，而不会破坏其表达。我们利用疟疾传播媒介的三个中肠特异性基因座的天然调控序列，来容纳一个原型抗疟分子和人工内含子中编码的指导 RNA，从而支持有效的基因驱动。我们评估了这些修饰对蚊子发育的干扰倾向及其对适应性的影响。由于这些特性的固有简单性和被动驱动模式，它们可能成为消除疟疾基因驱动测试途径的一部分。
