Editing thePlasmodium vivaxGenome, Using Zinc-Finger Nucleases
Open Access
- 31 July 2014
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Infectious Diseases
- Vol. 211 (1), 125-129
- https://doi.org/10.1093/infdis/jiu423
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.Keywords
This publication has 15 references indexed in Scilit:
- Targeting Plasmodium PI(4)K to eliminate malariaNature, 2013
- Malaria biology and disease pathogenesis: insights for new treatmentsNature Medicine, 2013
- Site-specific genome editing in Plasmodium falciparum using engineered zinc-finger nucleasesNature Methods, 2012
- Functional Analysis of Plasmodium vivax Dihydrofolate Reductase-Thymidylate Synthase Genes through Stable Transformation of Plasmodium falciparumPLOS ONE, 2012
- A genotype and phenotype database of genetically modified malaria-parasitesTrends in Parasitology, 2011
- Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architecturesNature Methods, 2010
- Plasmodium falciparum Sec24 marks transitional ER that exports a model cargo via a diacidic motifMolecular Microbiology, 2008
- Transient transfection of Plasmodium vivax blood stage parasitesMolecular and Biochemical Parasitology, 2006
- Antimalarial Activities of New Pyrrolo[3,2-f]Quinazoline-1,3-Diamine DerivativesAntimicrobial Agents and Chemotherapy, 2005
- Therapeutic Efficacies of Artesunate-Sulfadoxine-Pyrimethamine and Chloroquine-Sulfadoxine-Pyrimethamine in Vivax Malaria Pilot Studies: Relationship to Plasmodium vivax dhfr MutationsAntimicrobial Agents and Chemotherapy, 2002