Engineered Antiviral Sensor Targets Infected Mosquitoes.
Elena Dalla Benetta, Adam J López-Denman, Hsing-Han Li, Reem A Masri, Daniel J Brogan, Michelle Bui, Ting Yang, Ming Li, Michael Dunn, Melissa J Klein, Sarah Jackson, Kyle Catalan, Kim R Blasdell, Priscilla Tng, Igor Antoshechkin, Luke S Alphey, Prasad N Paradkar, Omar S Akbari
The CRISPR journal · 2023-Dec-19 · PMID 38108518 · DOI 10.1089/crispr.2023.0056Abstract
Escalating vector disease burdens pose significant global health risks, as such innovative tools for targeting mosquitoes are critical. CRISPR-Cas technologies have played a crucial role in developing powerful tools for genome manipulation in various eukaryotic organisms. Although considerable efforts have focused on utilizing class II type II CRISPR-Cas9 systems for DNA targeting, these modalities are unable to target RNA molecules, limiting their utility against RNA viruses. Recently, the Cas13 family has emerged as an efficient tool for RNA targeting; however, the application of this technique in mosquitoes, particularly Aedes aegypti , has yet to be fully realized. In this study, we engineered an antiviral strategy termed REAPER (vRNA Expression Activates Poisonous Effector Ribonuclease) that leverages the programmable RNA-targeting capabilities of CRISPR-Cas13 and its potent collateral activity. REAPER remains concealed within the mosquito until an infectious blood meal is uptaken. 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 viral prevalence of infection, and its promiscuous collateral activity can even kill infected mosquitoes within a few days. This innovative REAPER technology adds to an arsenal of effective molecular genetic tools to combat mosquito virus transmission.
Evidence profile
- Study type
- laboratory
- Text reviewed by the copilot
- Full text is available
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- published
- Corrections or retractions
- none
- Conflict statement
- O.S.A. is a founder of both Agragene, Inc. and Synvect, Inc., with equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. L.A is an adviser to Synvect, Inc. and Biocentis Ltd., with financial interest in both. All other authors declare no competing interests.