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Engineered Antiviral Sensor Targets Infected Mosquitoes

Dalla Benetta, Elena and López-Denman, Adam J. and Li, Hsing-Han and Masri, Reem A. and Brogan, Daniel J. and Bui, Michelle and Yang, Ting and Li, Ming and Dunn, Michael and Klein, Melissa J. and Jackson, Sarah and Catalan, Kyle and Blasdell, Kim R. and Tng, Priscilla and Antoshechkin, Igor and Alphey, Luke S. and Paradkar, Prasad N. and Akbari, Omar S. (2023) Engineered Antiviral Sensor Targets Infected Mosquitoes. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20230316-182416000.30

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Abstract

Escalating vector disease burdens pose significant global health risks, so innovative tools for targeting mosquitoes are critical. 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. 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.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2023.01.27.525922DOIDiscussion Paper
ORCID:
AuthorORCID
Dalla Benetta, Elena0000-0003-2556-8500
López-Denman, Adam J.0000-0001-6051-6381
Li, Hsing-Han0000-0003-4984-7942
Brogan, Daniel J.0000-0001-6582-8966
Bui, Michelle0000-0001-9198-8234
Yang, Ting0000-0001-7201-4231
Dunn, Michael0000-0001-8569-1725
Klein, Melissa J.0000-0002-5412-2340
Jackson, Sarah0000-0003-0388-6188
Catalan, Kyle0000-0003-4414-8608
Blasdell, Kim R.0000-0003-2121-0376
Tng, Priscilla0000-0002-6172-2600
Antoshechkin, Igor0000-0002-9934-3040
Alphey, Luke S.0000-0002-2916-3802
Paradkar, Prasad N.0000-0002-6553-2214
Akbari, Omar S.0000-0002-6853-9884
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. We thank Judy Ishikawa for mosquito husbandry assistance. This work was supported by funding from a DARPA Safe Genes Program Grant (HR0011-17-2-0047), and NIH awards (R01AI151004, DP2AI152071, and R21AI149161) awarded to O.S.A. We acknowledge the capabilities of the Australian Centre for Disease Preparedness (grid.413322.5) in undertaking this research, including infrastructure funded by the National Collaborative Research Infrastructure Strategy. Figures were created with BioRender.com. Data availability. All plasmids and annotated DNA sequence maps are available at www.addgene.com under accession numbers: 191374 (OA-1050T), 191375 (OA-1085F), 191376 (OA-1085L), 194001 (OA-1163A),194003(OA-1093B). Raw sequencing data are available at NCBI Sequence Read Archive (SRA), accession number PRJNA912231 (reviewer link: https://dataview.ncbi.nlm.nih.gov/object/PRJNA912231?reviewer=7ll0k7o7hauq2eh8kbv16mjbj9). Authors contributions. O.S.A., P.N.P. and E.D.B. conceived and designed the experiments. E.D.B., H.H.L., R.A.M., A.L.D., D.J.B., M.B., T.Y., M.L., I.A., performed molecular and genetic experiments. I.A. performed the RNA sequencing experiments and analysis. A.L.D., M.D., M.J.K., S.J., K.C., K.B. performed viral infection experiments and analysis. All authors contributed to the writing, analyzed the data, and approved the final manuscript. Competing Interest 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 each. All other authors declare no competing interests.
Funders:
Funding AgencyGrant Number
Defense Advanced Research Project Agency (DARPA)HR0011-17-2-0047
NIHR01AI151004
NIHDP2AI152071
NIHR21AI149161
DOI:10.1101/2023.01.27.525922
Record Number:CaltechAUTHORS:20230316-182416000.30
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20230316-182416000.30
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:120146
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:20 Mar 2023 20:27
Last Modified:20 Mar 2023 20:27

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