Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs.
Anna Buchman, Stephanie Gamez, Ming Li, Igor Antoshechkin, Hsing-Han Li, Hsin-Wei Wang, Chun-Hong Chen, Melissa J Klein, Jean-Bernard Duchemin, Prasad N Paradkar, Omar S Akbari
Proceedings of the National Academy of Sciences of the United States of America · 2019-Feb-26 · PMID 30723148 · DOI 10.1073/pnas.1810771116Abstract
Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive-based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered synthetic small RNAs targeting ZIKV is expressed and fully processed in Aedes aegypti , ensuring the formation of mature synthetic small RNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.
Evidence profile
- Study type
- laboratory
- Text reviewed by the copilot
- Full text is available
- Publication status
- published
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- none
- Conflict statement
- Conflict of interest statement: A.B. and O.S.A have submitted a provisional patent application on this technology. All other authors declare no competing financial interests.