With a strategy known as “population modification” that involves using a CRISPR-Cas9 gene propulsion system to introduce genes to prevent parasite transmission into mosquito chromosomes, researchers at the University of California (UC) have made a great leap forward in the use of genetic ones Technologies to control achieved the transmission of malaria parasites. Her work was published in the journal Nature Communications.
Adriana Adolfi, a postdoctoral fellow at the University of California at Irvine (UCI), worked with colleagues at UCI, UC Berkeley, and UC San Diego who had worked on CRISPR-based gene drive systems to make mosquito vectors resistant to the transmission of malaria parasites increase the effectiveness of the gene drive in female mosquito progeny. The team’s original gene drive, developed for the Indopakistani malaria vector mosquito Anopheles stephensi in 2015, was the first demonstration of a CRISPR-based gene drive in mosquitoes.
In this first study, published in the journal Proceedings of the National Academy of Sciences, gene drive was transmitted in approximately 99% of offspring when the parent in whom the gene drive was inserted was male, but only 60-70% the offspring if the parent into whom the gene drive was introduced was a female. A significant number of drive-resistant chromosomes are created in women; This could, in principle, allow these women to continue transmitting parasites.
Adolfi and coworkers solved the failure to drive women efficiently by equipping the gene drive with a functional copy of the target gene into which the drive was inserted. The normal function of this target gene in this species of mosquito is necessary for the survival and fertility of the woman after it has fed on blood, and its functionality is usually disrupted when the drive system is introduced into the gene. The resulting female mosquitoes showed strong and consistent drive and negligible production of drive-resistant chromosomes in a population cage study.
This strategy of inserting a gene drive into a gene essential to viability or fertility while including a functional gene that rescues the loss of viability or fertility offers a general solution to promote resistance in women. The new system also efficiently eliminates genetic errors that occur in the propulsion process.
“This work alleviates a major problem with early gene propulsion systems, namely the buildup of propulsion-resistant mosquitoes that can still transmit malaria parasites,” said UCI Professor Anthony James, a co-primary researcher on the study.
“The second generation gene propulsion system described in this article can be applied to any of the thousands of genes that are essential for insects to survive or reproduce,” added Ethan Bier, co-author of the study at UC San Diego. “While this system was developed in fruit flies, it can be easily transported to a wide variety of insect species that act as vectors for devastating diseases such as Chagas disease, sleeping sickness, leishmaniasis, and arbovirus diseases.”
The new gene propulsion system can now be used in combination with genes to block parasite transmission to develop field-ready mosquito strains, the researchers say. However, thorough testing is required to demonstrate safety and effectiveness before proceeding with field testing.
Caption: UCI vector biologist Anthony James. Photo credit: Steve Zylius / UCI.
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