Researchers at two campuses of University of California (UC) have reported in the journal Nature Scientific Reports a way to edit the genome of disease-carrying mosquitoes that marks a step closer to suppressing them on a continental scale.
The study used gene-editing technology known as clustered regularly interspaced short palindromic repeats associated protein 9, or CRISPR-Cas9, to insert and spread genes designed to suppress wild insects, while at the same time avoiding the resistance to these efforts that evolution would typically favor.
Funded by the U.S. National Institutes of Health (NIH), the University of California Institute for Mexico and the United States (UC MEXUS) and the Parker Foundation, the proof-of-concept study was demonstrated in fruit flies, an organism commonly used as a model in labs; but the researchers believe the technology could be used in mosquitoes to help fight malaria and other mosquito-borne diseases in the next decade.
The technology at the heart of the study is called a gene drive system, which manipulates how genetic traits are inherited from parent to offspring, according to a news release from UC Berkeley on Monday.
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 study based its calculations on a gene drive that past studies found could result in up to 99 percent of offspring inheriting the inserted gene. Yet the few offspring that don't inherit the gene present a big problem for this technology. A fraction of these offspring are immune to the gene drive, so any attempt to eliminate a mosquito species in this manner would result in a rapid rebound of those that are gene drive-immune.
To address this issue, the team devised a technique that they determined could potentially suppress mosquito species continent-wide.
The technique, called multiplexing, involves using one of the components of the CRISPR system, a guide ribonucleic acid (RNA), to target multiple locations in a gene at once. Computer modeling by the team suggests that the size of the population that could be suppressed increases exponentially with the number of these guide RNAs utilized. It also shows that with four or five multiplexed guide RNAs, a mosquito species could potentially be suppressed on a continental scale.
"What we showed is that, if you disrupt a gene required for fertility in female mosquitoes at multiple sites all at once, it becomes much harder for the population to evolve around that disruption. As a result, you can suppress a much larger population," said John Marshall, the study's lead author and an assistant professor of biostatistics and epidemiology at the UC Berkeley School of Public Health. "The potential of multiplexing is vast. With one guide RNA, we could suppress a room of mosquitoes. With four, we could potentially suppress a continent and the diseases they transmit."
The researchers now are working to adapt this technology to the mosquito species that transmit malaria, dengue and Zika.
"Knowing that we can potentially overcome the issues of resistance through careful engineering and multiplexing is huge," co-corresponding author Omar Akbari, an assistant professor of entomology at UC Riverside, was quoted as saying in the news release.
