DNA editing shows success in mosquito sterilization

Gene drive could eliminate malaria-carrying Anopheles gambiae

A new genetic tool may help eradicate Africa’s main malaria-carrying mosquitoes.  

A self-propagating cut-and-paste system known as a gene drive can sterilize female Anopheles gambiae mosquitoes, researchers report December 7 in Nature Biotechnology.

This is the second gene drive aimed at eliminating malaria. The first, published November 23 in the Proceedings of the National Academy of Sciences (SN Online: 11/23/15), would stop mosquitoes from transmitting the parasite. The new gene drive would eliminate the mosquitoes themselves by making it impossible for females to reproduce.

Gene drives are engineered pieces of DNA designed to slice a target gene and insert themselves. Like Star Trek’s Borg, gene drives assimilate every unaltered target gene they encounter. These ambitious bits of DNA break standard inheritance rules to get passed on to more than 50 percent of an altered animal’s offspring, “driving” themselves quickly through populations (SN: 12/12/15, p. 16).

Evolutionary geneticist Austin Burt of Imperial College London first conceived the idea of gene drives in 2003. For more than a decade, the drives remained mostly theoretical, but thanks to precision molecular scissors called CRISPR/Cas9, four gene drives, including the two in mosquitoes, were described this year.

“They all work terrifically,” says George Church, a geneticist at Harvard University.

Cas9 is a DNA-cutting enzyme borrowed from bacteria. Researchers can design RNA molecules to guide the enzyme to particular genes.

Church is pleased to see that this latest mosquito gene drive works, but says further modifications may be needed before it is ready for release in the field.

Researchers may also want to combine approaches, first releasing a gene drive that would prevent mosquitoes from carrying malaria, then later releasing one to control mosquito populations, Church suggests.

In the new study, Burt and colleagues first used CRISPR/Cas9 and another type of gene editor known as TALENs to disrupt each of three genes that are active at high levels in mosquito ovaries. Females carrying two copies of any one of the three disrupted genes were sterile. Once the researchers had confirmed that messing with the genes would make the mosquitoes sterile, the team built gene drives to insert into the genes.

Under normal circumstances, only 50 percent of progeny would inherit any given gene. With the gene drives, 76.1 percent to 99.6 percent of the offspring inherited the drive, the researchers found.

This gene drive had some technical glitches, so it won’t be the final version that researchers would release to control wild mosquito populations. But the researchers are hopeful that future gene drives could curb populations of A. gambiae, says study coauthor Tony Nolan, a molecular biologist at Imperial College London. “We need new approaches for vector control, and this is a promising one.”

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