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Roberto R. Moraes Barros, Judith Straimer, Juliana M. Sa, Rebecca E. Salzman, Viviana A. Melendez-Muniz, Jianbing Mu, David A. Fidock, Thomas E. Wellems, Editing the Plasmodium vivax Genome, Using Zinc-Finger Nucleases, The Journal of Infectious Diseases, Volume 211, Issue 1, 1 January 2015, Pages 125–129, https://doi.org/10.1093/infdis/jiu423
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Abstract
Plasmodium vivax is a major cause of malaria morbidity worldwide yet has remained genetically intractable. To stably modify this organism, we used zinc-finger nucleases (ZFNs), which take advantage of homology-directed DNA repair mechanisms at the site of nuclease action. Using ZFNs specific to the gene encoding P. vivax dihydrofolate reductase (pvdhfr), we transfected blood specimens from Saimiri boliviensis monkeys infected with the pyrimethamine (Pyr)–susceptible Chesson strain with a ZFN plasmid carrying a Pyr-resistant mutant pvdhfr sequence. We obtained Pyr-resistant parasites in vivo that carried mutant pvdhfr and additional silent mutations designed to confirm editing. These results herald the era of stable P. vivax genetic modifications.