Gene drives are used to bias genetic inheritance in favor of rapidly spreading, self-destructive genes and could be an environmentally friendly and cost-effective way to suppress populations of disease-spreading insects. The rise of CRISPR/Cas9 gene-editing technology has recently revolutionized gene-drive systems because it offers a rapid, efficient, and reliable way to make precise, targeted changes to the genome.

The new study based its calculations on past gene-drive findings that resulted in up to 99% of offspring inheriting the inserted gene. However, the few offspring that don't inherit the gene present a big problem for this technology. Since a fraction of these offspring is immune to the gene drive, any attempt to eliminate a mosquito species in this manner would result in a rapid rebound of those that are gene-drive immune. The impact of this resistance on the ability of gene drive to spread and suppress populations had previously been discussedbut had not been thoroughly evaluated.

The mathematical modeling that the investigators utilized found that the gene-driveevolved resistance would have a major impact on attempts to eliminate a mosquito species on a continent-wide scale. To address this issue, the research team devised a technique that they determined could potentially suppress mosquito species continent-wide.

Employing a strategy called multiplexing, which involves using one of the components of the CRISPR system, a gRNA, to target multiple locations in a gene at once, the research team suggested that the size of the population that could be suppressed increases exponentially with the number of these gRNAs utilized. It also shows that with four or five multiplexed gRNAs, a mosquito species could potentially be suppressed on a continental scale.

"Knowing that we can potentially overcome the issues of resistance through careful engineering and multiplexing is huge," noted senior study investigator Omar Akbari, Ph.D., assistant professor of entomology at UC Riverside.

The researchers demonstrated the technology was feasible using a fruit fly model. Now they are working to adapt this technology to the mosquito species that transmit malaria, dengue, and Zika.

"The potential of multiplexing is vast. With one gRNA, we could suppress a room of mosquitoes," Dr. Marshall concluded. With four, we could potentially suppress a continent and the diseases they transmit. But nature has a knack for finding a way around hurdles, so assessing that potential will require a lot more work."

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Avoiding CRISPR-Mediated Gene-DriveEvolved Resistance in Mosquitoes - Genetic Engineering & Biotechnology News (blog)