While introducing genetic changes has long been supported by advancing technologies, getting those modifications to spread through wild mosquito populations has remained a challenge. Now, the newly understood concept of gene drive, in which genetic elements can spread more rapidly than those following traditional Mendelian inheritance principles, may finally solve the problem.
HOW GENE DRIVE WORKS
HOW GENE DRIVES SPREAD
Without gene drive, an allele will be passed from generation to generation via traditional Mendelian genetics. That is, when a heterozygous individual carrying only one copy of the allele mates with an individual lacking it altogether, only half of their offspring will inherit the genetic segment. But in a gene drive that spreads the allele to the homologous chromosome in the germline, all progeny will receive a copy. With gene drive, it’s even possible for a deleterious allele to spread through the population, despite imposing a severe fitness cost.
HOW GENE DRIVE COULD BE USED TO CONTROL MALARIA
There are three general approaches to implementing gene drives in mosquito populations for the control of malaria: (1) spread a deleterious mutation to reduce mosquito numbers, (2) distort the sex ratio of the population, or (3) deliver cargo to render mosquitoes resistant to the malaria parasite.
(2) SKEWED SEX RATIO
A gene drive designed to selectively destroy the X chromosome in Anopheles gambiae sperm will result in the nonviability of those sperm, leaving only sperm carrying Y chromosomes. This will lead to a sex ratio greatly skewed toward males, which will eventually cause the population to crash.
(3) POPULATION-WIDE GENE KNOCK-IN
A gene drive can also be designed to deliver a cargo, such as an antimicrobial peptide, that makes mosquitoes resistant to the malaria parasite. In this case, the antimalarial cargo would be expressed wherever the parasite is most vulnerable, whereas germline expression of the gene drive would guarantee its spread through the population.
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