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The first CRISPR-based gene drives in mosquitoes that carry dengue fever and other arboviruses were described last month in the open-access journal eLife.
The findings, originally posted on bioRxiv* could help speed up the development of gene drives that safely control wild populations of the mosquito Aedes aegypti (Ae. aegypti) to help fight the local spread of disease.
Ae. aegypti is the main carrier for many arboviruses that increasingly infect millions of people every year. Due to the high annual incidence of dengue fever and other diseases carried by this mosquito, along with the associated economic burdens and lack of effective vaccines, there is increasing interest in creating new population-control methods to prevent pathogen transmission.
“The use of gene drives has sparked significant enthusiasm for the genetic control of mosquitoes,” explains lead author Ming Li, Postdoctoral Scholar in Cell and Developmental Biology at the University of California, San Diego, US. “But until now, no such system has been developed in Ae. aegypti.”
To fill this void, Li and the team developed several gene drives for use in these mosquitoes to spread disease-refractory genes into the population. These systems involved adding two unlinked components, Cas9 and a guide RNA, separately in the genome, in a ‘split drive’ design to ensure greater safety and confinability.
After demonstrating the efficiency of their split-gene drives, the team applied mathematical modelling that suggests their drives are valuable for several reasons. These include the fact that several consecutive releases of male mosquitoes carrying the split drive and anti-pathogen cargo, at an achievable one-to-one ratio with the wild population, could help spread disease resistance into these populations.
“We also found that our split drives should not spread significantly into neighbouring populations, and could be removed from the main population on a timescale fitting with local arbovirus elimination,” explains senior author Omar Akbari, Associate Professor of Cell and Developmental Biology at the University of California, San Diego.
Akbari notes that progress in the gene-drive field, and the potential of these drives to spread globally, have “understandably” led to more prominent discussions around the ethics, risks, governance and guidance for their use. Speaking about the systems developed by his own team, he adds: “The highly desirable features of our split drives in Ae. aegypti, including the fact they allow users greater control, may be important for gaining wider acceptance and regulatory approval for them as responsible strategies for eliminating pathogens spread by this mosquito species.”
*This study was originally posted on bioRxiv at https://www.biorxiv.org/content/10.1101/645440v1.
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