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Scientists Report Proof-of-Concept CRISPR/Cas9 Gene Drive in Malaria-Carrying Mosquito

NEW YORK (GenomeWeb) – Scientists from the University of California, San Diego and UC-Irvine have created a proof-of-concept, CRISPR/Cas9-based gene drive to genetically modify entire populations of the malaria-carrying mosquito Anopheles stephensi.

Led by co-first authors Valentino Gantz of UCSD and Nijole Jasinskiene of UC-Irvine, and senior authors Ethan Bier and Anthony James of UC-Irvine, the scientists adapted a mutagenic chain reaction gene drive to spread genes conferring resistance to the malaria parasite Plasmodium falciparum.

The drive is constructed as a plasmid carrying a Cas9 protein optimized for use in A. stephensi, guide RNA targeting an insertion site, and templates of both antimalarial effector genes as well as marker genes to be inserted into the genome following homology directed repair.

The scientists said they were able to achieve target gene conversion with more than 99.5 percent efficiency.  

A. stephensi accounts for approximately 12 percent of malaria cases in India, with a total of about 106,000 cases in 2014. Until the advent of CRISPR/Cas9 genome editing, gene drives had been a largely theoretical construct, but malaria transmission has been an exemplar of a potential application of the idea. Last year, scientists led by Kevin Esvelt and George Church of Harvard Medical School published a sketch of how to build a gene drive with CRISPR/Cas9, and last week those two scientists led a study which demonstrated a reversible gene drive in yeast.

The new A. stephensi gene drive is adapted from a technology first used to spread mutations in Drosophila melanogaster, developed by Gantz and Bier and published in March in Science.

The new publication offered insight into a number of issues specific to gene drive technology, such as transmission rates in both male and female germline and somatic cells. But broadly, the scientists wrote that the study "[justifies] a degree of optimism for the future successful application of this technology."

The authors also acknowledged the necessity for much more research before such a technology could be applied to wild populations, and that stakeholders should simultaneously develop new regulatory structures, modes of communicating with potentially affected communities, and other methods to eradicate malaria.