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Engineered Mosquitoes Could Eliminate Deadly Malaria Strain

ByTim De ChantNOVA NextNOVA Next

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Human-engineered, malaria-resistant mosquitoes could be ready for field tests in less than a year.

Scientists now have all the pieces in place to release mosquitoes into the wild with traits that would could eliminate them as vectors for

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Plasmodium falciparum , the parasite that causes malaria. The new study merges the CRISPR-Cas9 gene editing system with gene drives, the so-called selfish genes that ensure subsequent generations retain a given trait.

Anopheles stephensi

Mosquitoes reproduce fast enough that the required traits could spread throughout a wild population in as few as five years.

Back when we first reported on the CRISPR-Cas9-gene drive combination back in July 2014, the potential was clear:

“This is one of the most exciting confluences of different theoretical approaches in science I’ve ever seen,” says Arthur Caplan, a bioethicist at New York University. “It merges population genetics, genetic engineering, molecular genetics, into an unbelievably powerful tool.”

There was also a measure of caution at the time, too. Researchers working on CRISPR-Cas9-based gene drives had all the pieces in place, but they were hesitant to combine them. The power to change entire wild populations is, of course, not to be taken lightly.

gene-drive-family-tree
A gene drive (blue) always ends up in all offspring, even if only one parent has it. That means that, given enough generations, it will eventually spread through the entire population.

The research team behind the new study, published in the Proceedings of the National Academy of Science, was led by Valentino Gantz, Ethan Bier, and Anthony James, all at the University of California, Irvine. They tested their system in Anopheles stephensi , a malaria vector that inhabits the Indian subcontinent. They endowed the mosquitoes with genes for antibodies that would attack the malaria parasite. Here are Heidi Ledford and Ewan Callaway, reporting for Nature:

For Anthony James, a molecular biologist at the University of California, Irvine, and an author of the paper, such a release would spell the end of a 30-year quest to use mozzie genetics to squash malaria.

James and his laboratory have painstakingly built up the molecular tools to reach this goal. They have worked out techniques for creating transgenic mosquitoes — a notoriously challenging endeavour — and isolated genes that could confer resistance to P. falciparum . But James lacked a way to ensure that those genes would take hold in a wild population.

What he was missing were gene drives, a combination initially proposed in the literature by Kevin Esvelt, a researcher at Harvard University. Gantz and Bier lent their expertise in this study. Gene drives copy themselves from one chromosome in a pair to the other using a sort of molecular scissors known as an endonuclease. When a cell’s repair machinery notices the break, it use the original sequence to mend the break.

The trick is that anything that’s inside the gene drive’s sequence gets copied into the second chromosome, giving the cell has two copies of the drive and any contained traits. If those edits are made to the sperm and egg cells, they’ll be passed on to the next generation at a rate of 100%. The UC-Irvine team’s results approached that theoretical maximum, with 99.5% of offspring containing the edited genes.

For now, Gantz, Bier, and James are not planning to release their creation into the wild. Rather, they said, they’ll wait for society to decide whether it’s worth it. And that decision likely won’t happen until we have a better handle on any potential risks.

Photo credit: Tony James (UCI), Esvelt et al 2014