Editing the Plasmodium vivax Genome, Using Zinc-Finger Nucleases

Editing the Plasmodium vivax Genome, Using Zinc-Finger Nucleases
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DOI:
10.1093/infdis/jiu423
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发表时间:
2015-01-01
影响因子:
6.4
通讯作者:
Wellems, Thomas E.
Wellems, Thomas E.
中科院分区:
医学2区
文献类型:
--
作者:
Barros, Roberto R. Moraes;Straimer, Judith;Wellems, Thomas E.

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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.