Newswise — Genetically engineered mosquitoes are resistant to multiple types of dengue virus (DENV), according to a study published January 16 in the open-access journal PLOS Pathogens by Prasad Paradkar of the Australian Animal Health Laboratory, and Omar Akbari of the University of California, San Diego, and colleagues. As noted by the authors, this is the first engineered approach that targets all types of DENV, which is crucial for effective disease suppression.
Dengue is a mosquito-borne viral disease that represents a pressing global problem, and new solutions are needed to prevent its transmission. DENV is mainly transmitted by Aedes aegypti mosquitoes. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. In the new study, the authors describe the development of A. aegypti mosquitoes synthetically engineered to be resistant to multiple types of DENV.
These mosquitoes express a gene encoding an engineered single-chain variable fragment (scFv) derived from a broadly neutralizing DENV human monoclonal antibody. Mosquitoes expressing the anti-DENV scFv cannot be infected with or transmit any of the four types of DENV, so they should not be able to transmit the virus to humans. Taken together, these results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail related viruses. According to the authors, this strategy could be coupled with a gene-drive system to rapidly convert wild mosquito populations into genetically modified mosquitoes that would be completely resistant to DENV transmission.
Akbari adds, “The most important aspect of this study is the fact that we engineered mosquitoes to be refractory to all major serotypes of Dengue virus. This may serve as a genetic tool to control Dengue in the wild in the future.
Funding: This work was supported in part by a Defense Advanced Research Project Agency (DARPA) Safe Genes Program Grant (HR0011-17-2- 0047) awarded to O.S.A. and a NIH Exploratory/Developmental Research Grant Award (1R21AI123937) awarded to O.S.A and CSIRO internal funding to P.N.P. The funders had no role in study design, data collection, analysis, the decision to publish, nor the preparation of the manuscript.
Competing Interests: O.S.A is a founder and serves on the scientific advisory board for Agragene. J.E.C. has served as a consultant for Takeda Vaccines, Sanofi Pasteur, Pfizer, and Novavax, is on the Scientific Advisory Boards of CompuVax, GigaGen, Meissa Vaccines, and is the Founder of IDBiologics, Inc. All other authors declare no competing financial interests.
Citation: Buchman A, Gamez S, Li M, Antoshechkin I, Li H-H, Wang H-W, et al. (2020) Broad dengue neutralization in mosquitoes expressing an engineered antibody. PLoS Pathog 16(1): e1008103. https://doi.org/10.1371/
Image Credit: Buchman A, et al. (2020)
Image Caption: A swarm of mosquitoes hover near an infected blood meal opportunity. Glowing transgenic mosquitoes have a protective DNA barrier that prevents them from supporting blue dengue virus (DENV) particle replication. In contrast, unprotected wildtype mosquitoes are able to become infected and transmit DENV. A unique antibody-expressing transgene has the ability to provide resistance against four different DENV serotypes.
Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California, United States of America
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, United States of America
Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Zhunan, Taiwan
CSIRO Health and Biosecurity, Australian Animal Health Laboratory, Geelong, VIC, Australia
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
Departments of Pediatrics, Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
Tata Institute for Genetics and Society-UCSD, La Jolla, California, United States of America
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