Benetta Elena Dalla, López-Denman Adam J, Li Hsing-Han, Masri Reem A, Brogan Daniel J, Bui Michelle, Yang Ting, Li Ming, Dunn Michael, Klein Melissa J, Jackson Sarah, Catalan Kyle, Blasdell Kim R, Tng Priscilla, Antoshechkin Igor, Alphey Luke S, Paradkar Prasad N, Akbari Omar S
School of Biological Sciences, Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, 92093, USA.
CSIRO Health and Biosecurity, Australian Centre for Disease Preparedness, Geelong, VIC 3220, AU.
bioRxiv. 2023 Jan 27:2023.01.27.525922. doi: 10.1101/2023.01.27.525922.
Escalating vector disease burdens pose significant global health risks, so innovative tools for targeting mosquitoes are critical. We engineered an antiviral strategy termed REAPER (vNA xpression ctivates oisonous ffector ibonuclease) that leverages the programmable RNA-targeting capabilities of CRISPR Cas13 and its potent collateral activity. Akin to a stealthy Trojan Horse hiding in stealth awaiting the presence of its enemy, REAPER remains concealed within the mosquito until an infectious blood meal is up taken. Upon target viral RNA infection, REAPER activates, triggering programmed destruction of its target arbovirus such as chikungunya. Consequently, Cas13 mediated RNA targeting significantly reduces viral replication and its promiscuous collateral activity can even kill infected mosquitoes. This innovative REAPER technology adds to an arsenal of effective molecular genetic tools to combat mosquito virus transmission.
不断升级的媒介传播疾病负担构成了重大的全球健康风险，因此用于靶向蚊子的创新工具至关重要。我们设计了一种名为REAPER（病毒核酸表达激活毒性效应核糖核酸酶）的抗病毒策略，该策略利用了CRISPR Cas13的可编程RNA靶向能力及其强大的附带活性。REAPER就像一匹隐藏在暗处等待敌人出现的隐形特洛伊木马，在蚊子摄取感染性血餐之前一直隐藏在蚊子体内。一旦目标病毒RNA感染，REAPER就会激活，触发对其目标虫媒病毒（如基孔肯雅病毒）的程序性破坏。因此，Cas13介导的RNA靶向显著降低了病毒复制，其混杂的附带活性甚至可以杀死被感染的蚊子。这种创新的REAPER技术为对抗蚊子病毒传播的有效分子遗传工具库增添了新内容。
