New, efficient CRISPR-based gene drive strategy to regulate the transmission of malaria parasites

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Using a strategy known as “population modification,” which involves using a CRISPR-Cas9 gene propulsion system to introduce genes that prevent parasite transmission into mosquito chromosomes, University of California researchers have made a great leap forward in the use of genetic technologies for the Control of the transmission of made malaria parasites.

Postdoctoral researcher Adriana Adolfi of the University of California at Irvine, working with colleagues from UCI, UC Berkeley and UC San Diego, continued the group’s pioneering work to develop CRISPR-based gene drive systems that can help mosquito vectors become resistant to the transmission of malaria parasites of the genetic drive in female mosquito progeny.

“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 vector biologist Anthony James, Donald Bren Professor of Microbiology and Molecular Genetics and Molecular Biology & Biochemistry, who as Co-Primary Investigator was involved in the study.

The second generation gene propulsion system described in this article can be applied to any of the several thousand genes that are essential to the survival or reproduction of insects. While developed in fruit flies, this system is easily transportable to a wide variety of insect species that act as vectors for devastating disorders such as Chagas disease, sleeping sickness, leishmaniasis, and arbovirus diseases. “

Ethan Bier, UC San Diego Distinguished Professor, co-author of the Director of Studies and Science at the Tata Institute for Genetics and Society

The study results appear in Nature Communications. Link to the course: https://www.nature.com/articles/s41467-020-19426-0

They describe a highly efficient version of the team’s second generation of the original gene drive that was developed for the Indopakistani malaria vector mosquito Anopheles stephensi. The work, published in 2015 in Proceedings of the National Academy of Sciences, was the first demonstration of a CRISPR-based gene drive in mosquitoes.

In this first study, the gene drive was transmitted to about 99 percent of the offspring if the parent the gene drive was inserted into was a male, but only 60 to 70 percent of the offspring if the parent who the gene drive was inserted into was a male. was female. A significant number of drive-resistant chromosomes are created in women; This could, in principle, allow these women to continue transmitting parasites.

Adolfi, lead author of the new study, and coworkers solved the failure to drive efficiently by women by equipping the gene engine with a functional copy of the target gene into which the engine 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 for 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. As with a catalytic converter that removes combustion pollution from automobiles, the new system also eliminates genetic errors that occur in propulsion.

This gene propulsion system can now be used in combination with genes to block parasite transmission to develop field-ready mosquito strains. Thorough testing is required to demonstrate safety and effectiveness before proceeding with field testing.

Source:

University of California – Irvine

Journal reference:

Adolfi, A., et al. (2020) Efficient population modification gene drive rescue system in the malaria mosquito Anopheles stephensi. Nature communication. doi.org/10.1038/s41467-020-19426-0.

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