Tackling Zika Transmission at the Source With Genetically Engineered Resistant Mosquitoes

As several Zika virus vaccine candidates undergo clinical trials, a group of investigators is taking an alternate approach to quell transmission by genetically engineering mosquitoes to be resistant to the virus.

In a new study published in the journal Proceedings of the National Academy of Sciences (PNAS), a team from the University of California, San Diego, collaborated with investigators in Australia and Taiwan and used genomic technology to generate a mosquito that is resistant to Zika virus.

“Transgenic-based (and specifically synthetic small RNA- based) methods for making disease-refractory mosquitoes can be quite effective,” Anna B. Buchman, PhD, research data analyst at Akbari Lab, Division of Biological Sciences, University of California, San Diego, and lead investigator on the study, told Contagion^®.

“There have been previous efforts to use transgenes in general, and miRNAs in particular, to render mosquitoes refractory to several mosquito-borne diseases (although never ZIKV), however, many of them were not 100% effective,” she continued. “What we really saw with our study was that, with some optimization, it is really possible to make mosquitoes that are 100% resistant to a disease and still have high fitness.”

To do that, investigators took Aedes aegypti mosquitoes at the embryonic stage and injected them with an anti-Zika gene and another gene that expresses red eyes in order to tell the modified ones apart. The engineered mosquitoes displayed lower levels of viral infection, dissemination, and transmission.

“Our results demonstrate that engineered mosquitoes express a polycistronic cluster of synthetic small RNAs designed to target the ZIKV genome. As a result, homozygous mosquitoes were refractory to ZIKV infection, and therefore could not transmit the virus,” the investigators wrote.

This strategy of vector control could one day replace the wild populations of the Aedes aegypti mosquito, according to the investigators.

“Further investigation of this technology is needed before we could look at taking this beyond the lab. There are certain technologies available, like gene drive, which could be used to penetrate the wild population with these mosquitoes. This would require breeding a large number of these mosquitoes in a lab and releasing them in affected regions to stop transmission,” Prasad N. Paradkar, PhD, research scientist at CSIRO Health and Biosecurity, Australian Animal Health Laboratory, and co-author of the study, told Contagion^®.

“However, we’re not at that stage yet,” Dr. Paradkar continued. “We need to conduct further experiments and risk analysis around the ecological safety of this work, and there would need to be well-informed public discussion and community engagement around this possible avenue, alongside with the necessary regulatory approvals.”

Dr. Buchman believes future research should focus on both vector control and alternative prevention measures.

“Ultimately, given the impact of these diseases, the mosquito is the deadliest animal in the world, and millions of people all over the world suffer because of the diseases this animal spreads,” she said. “Researchers and clinicians need to work together to develop multi-pronged approaches to try to control these diseases.”