Garrood William T, Cuber Piotr, Willis Katie, Bernardini Federica, Page Nicole M, Haghighat-Khah Roya E
Department of Life Sciences, Imperial College London, London, United Kingdom.
Department of Molecular Biology, Core Research Laboratories, Natural History Museum, London, United Kingdom.
Front Genet. 2022 Oct 19;13:891218. doi: 10.3389/fgene.2022.891218. eCollection 2022.
The last century has witnessed the introduction, establishment and expansion of mosquito-borne diseases into diverse new geographic ranges. Malaria is transmitted by female mosquitoes. Despite making great strides over the past few decades in reducing the burden of malaria, transmission is now on the rise again, in part owing to the emergence of mosquito resistance to insecticides, antimalarial drug resistance and, more recently, the challenges of the COVID-19 pandemic, which resulted in the reduced implementation efficiency of various control programs. The utility of genetically engineered gene drive mosquitoes as tools to decrease the burden of malaria by controlling the disease-transmitting mosquitoes is being evaluated. To date, there has been remarkable progress in the development of CRISPR/Cas9-based homing endonuclease designs in malaria mosquitoes due to successful proof-of-principle and multigenerational experiments. In this review, we examine the lessons learnt from the development of current CRISPR/Cas9-based homing endonuclease gene drives, providing a framework for the development of gene drive systems for the targeted control of wild malaria-transmitting mosquito populations that overcome challenges such as with evolving drive-resistance. We also discuss the additional substantial works required to progress the development of gene drive systems from scientific discovery to further study and subsequent field application in endemic settings.
上个世纪见证了蚊媒疾病传入、确立并扩展到各种新的地理区域。疟疾由雌蚊传播。尽管在过去几十年里减轻疟疾负担方面取得了巨大进展，但目前传播率再度上升，部分原因是蚊子对杀虫剂产生抗药性、出现抗疟药物耐药性，以及最近新冠疫情带来的挑战，导致各种防控计划的实施效率降低。利用基因工程基因驱动蚊子作为控制传播疾病蚊子以减轻疟疾负担的工具正在接受评估。迄今为止，由于原理验证和多代实验取得成功，基于CRISPR/Cas9的归巢内切酶设计在疟蚊开发方面取得了显著进展。在本综述中，我们研究了从当前基于CRISPR/Cas9的归巢内切酶基因驱动开发中吸取的经验教训，为开发基因驱动系统提供了一个框架，以有针对性地控制野生疟蚊种群，克服诸如不断演变的驱动抗性等挑战。我们还讨论了将基因驱动系统从科学发现推进到进一步研究以及随后在流行地区进行实地应用所需开展的更多实质性工作。
