Creative Minds: Building a CRISPR Gene Drive Against Malaria

Valentino Gantz

Valentino Gantz/Credit: Erik Jepsen

Researchers have used Drosophila melanogaster, the common fruit fly that sometimes hovers around kitchens, to make seminal discoveries involving genetics, the nervous system, and behavior, just to name a few. Could a new life-saving approach to prevent malaria be next? Valentino Gantz, a researcher at the University of California, San Diego, is on a path to answer that question.

Gantz has received a 2016 NIH Director’s Early Independence Award to use Drosophila to hone a new bioengineered tool that acts as a so-called “gene drive,” which spreads a new genetically encoded trait through a population much faster than would otherwise be possible. The lessons learned while working with flies will ultimately be applied to developing a more foolproof system for use in mosquitoes with the hope of stopping the transmission of malaria and potentially other serious mosquito-borne diseases.

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Gene Drive Research Takes Aim at Malaria

Mosquitoes and a Double HelixMalaria has afflicted humans for millennia. Even today, the mosquito-borne, parasitic disease claims more than a half-million lives annually [1]. Now, in a study that has raised both hope and concern, researchers have taken aim at this ancient scourge by using one of modern science’s most powerful new technologies—the CRISPR/Cas9 gene-editing tool—to turn mosquitoes from dangerous malaria vectors into allies against infection [2].

The secret behind this new strategy is the “gene drive,” which involves engineering an organism’s genome in a way that intentionally spreads, or drives, a trait through its population much faster than is possible by normal Mendelian inheritance. The concept of gene drive has been around since the late 1960s [3]; but until the recent arrival of highly precise gene editing tools like CRISPR/Cas9, the approach was largely theoretical. In the new work, researchers inserted into a precise location in the mosquito chromosome, a recombinant DNA segment designed to block transmission of malaria parasites. Importantly, this segment also contained a gene drive designed to ensure the trait was inherited with extreme efficiency. And efficient it was! When the gene-drive engineered mosquitoes were mated with normal mosquitoes in the lab, they passed on the malaria-blocking trait to 99.5 percent of their offspring (as opposed to 50 percent for Mendelian inheritance).

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Fighting Malaria, With a Little Help from Bacteria

photo of a red-bellied mosquito adjacet to a photo of pink blobs

Caption: Anopheles female blood feeding and Plasmodium falciparum eggs in Anopheles mosquito midguts.
Credit: Image courtesy of Jose Luis Ramirez, Laboratory of Malaria and Vector Research, NIAID, NIH

It turns out that one of the most innovative and effective strategies to fight malaria might involve harnessing a bacterium called Wolbachia. This naturally occurring genus of bacteria infects many species of insects, including mosquitoes. The reason this is important is that Wolbachia-infected mosquitoes become resistant to the parasite Plasmodium falciparum, which causes some 219 million cases of malaria worldwide and more than 660,000 deaths [1]. Wouldn’t it be amazing if Wolbachia-infected mosquitoes blocked the transmission of malaria?

Unfortunately, Wolbachia don’t normally pass from generation to generation in Anopheles, the mosquitoes that spread malaria. But that hurdle has now been overcome. Continue reading