A team of researchers, including two from the University of California, Riverside, have made a key discovery that could potentially help eliminate disease-spreading mosquitoes on a continent-wide scale.
Gene drives have been proposed as an inexpensive, environmentally friendly, and long-lasting way to address significant ecological and public health-related problems, including mosquito-borne diseases such as malaria, Zika virus, dengue fever, yellow fever, and others.
There are different types of gene drives that vary in their inheritance mechanisms, including a type known as homing-based gene drive, which can be used to suppress populations. Past studies have found that the homing-based method can result in 90 to 99 percent of offspring inheriting the altered gene structure, as opposed to the 50 percent expected with traditional genetics, making this system extraordinarily powerful.
Although the high inheritance rate seen with these homing systems is quite promising, the small percentage of offspring that don’t inherit the genetic change are problematic because they can prevent the genetically changed population of an organism from taking over a region.
In work outlined in the bioRxiv article, the researchers used mathematical modeling to determine that resistant alleles will have a major impact on attempts to get rid of a species of mosquito on a scale of a continent such as Africa. In other words, an attempt to eliminate a species of mosquito using this technique would result in a rapid rebound of the suppressed population of mosquitoes due to resistance alleles.
To address this issue, the researchers devised and validated a technique that involves multiplexing guide RNAs within the gene drive. Multiplexing means targeting multiple locations in a gene with the guide RNAs.
Modeling by the research team suggests that the size of the population that can be suppressed increases exponentially with the number of multiplexed guide RNAs. It also shows that with six multiplexed guide RNAs, a mosquito species could potentially be suppressed on a continental scale.
The researchers also demonstrated successful multiplexing in a fruit fly (Drosophila melanogaster), an organism commonly used as a model in labs. Now, they are working to adapt that same technique to mosquitoes.
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