Engineered Antiviral Sensor Targets Infected Mosquitoes.

Autor:	Dalla Benetta E; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, California, USA., López-Denman AJ; CSIRO Health and Biosecurity, Australian Centre for Disease Preparedness, Geelong, Australia., Li HH; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, California, USA., Masri RA; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, California, USA., Brogan DJ; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, California, USA., Bui M; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, California, USA., Yang T; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, California, USA., Li M; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, California, USA., Dunn M; CSIRO Health and Biosecurity, Australian Centre for Disease Preparedness, Geelong, Australia., Klein MJ; CSIRO Health and Biosecurity, Australian Centre for Disease Preparedness, Geelong, Australia., Jackson S; CSIRO Health and Biosecurity, Australian Centre for Disease Preparedness, Geelong, Australia., Catalan K; CSIRO Health and Biosecurity, Australian Centre for Disease Preparedness, Geelong, Australia., Blasdell KR; CSIRO Health and Biosecurity, Australian Centre for Disease Preparedness, Geelong, Australia., Tng P; Arthropod Genetics, The Pirbright Institute, Pirbright, United Kingdom., Antoshechkin I; Division of Biology and Biological Engineering (BBE), California Institute of Technology, Pasadena, California, USA., Alphey LS; Arthropod Genetics, The Pirbright Institute, Pirbright, United Kingdom.; Department of Biology, University of York, York, United Kingdom., Paradkar PN; CSIRO Health and Biosecurity, Australian Centre for Disease Preparedness, Geelong, Australia., Akbari OS; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
Jazyk:	angličtina
Zdroj:	The CRISPR journal [CRISPR J] 2023 Dec; Vol. 6 (6), pp. 543-556.
DOI:	10.1089/crispr.2023.0056
Abstrakt:	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.
Databáze:	MEDLINE
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