Targeting the malaria parasite genome

The use of targeted nucleases to modify the genome of the malaria parasite Plasmodium falciparum is reported this week in a paper published in Nature Methods. This will enable genetic studies, including on drug resistance mechanisms, of this important human parasite.

Millions of people worldwide suffer from malaria, and drug resistance is a widespread problem in fighting the disease. Research on the protozoan parasites that cause malaria has been held back because of the lack of robust research tools, particularly those for manipulating the genome of these organisms.

Zinc-finger nucleases (ZFNs) can be designed to cleave and, consequently, to make changes at desired locations in the genomes of many species. They have been previously used to modify the genomes of flies, fish, yeast, worms, mice, rats and human cells, among others.

David Fidock and colleagues report the use of these tools to modify the genome of the most lethal malaria parasite, P. falciparum. The parasite differs from other organisms in the nucleotide balance of its genome as well as in some aspects of its endogenous DNA repair machinery-factors that could have impaired the efficacy of ZFNs. But Fidock and colleagues show that these tools can be effectively used to manipulate the Plasmodium genome and use ZFNs to delete parasite genes, to replace one gene with another, and to make changes in gene sequence in an efficient and rapid manner.