Gene drives tested against real-world malaria diversity
Gene drive technology, which uses genetic engineering to spread selected genes through a population, is a potential strategy for blocking the spread of malaria, either by suppressing mosquito populations or rendering them incapable of transmitting the disease. However, genetically driven mosquitoes have mainly been tested in the laboratory with mosquitoes that are ten years old. Plasmodium parasite strains, and it is not known whether they can block the transmission of genetically diverse diseases. Plasmodium now in circulation. In an important step toward application, Habtewold et al. now report Nature the adaptation of a previously developed gene drive strategy to an African context.
The gene drive strategy involves the introduction of antiparasitic effectors into the mosquito genome, which are propagated within populations using a synthetic gene drive based on the Cas9 endonuclease. In this design, the antiparasitic and gene drive effector functions are separated into two strains. The transmission-blocking antiparasitic modification, called MM-CP, involves two antimicrobial peptides, magainin 2 from the African frog and melittin from the European bee, expressed from the endogenous zinc carboxypeptidase A1 gene (CP). To take this work out of the laboratory, the authors built a secure facility in Tanzania, in which they then established a colony carrying the antimalarial transgene MM-CP and a helper strain (carrying Cas9), both inside the local Ifakara mosquito strain. MM-CP mosquitoes were then fed genetically diverse substances P. falciparum isolates collected from infected children. They showed reduced oocyst growth and sporozoite production with delayed migration to the salivary glands, which validated previous laboratory work.
