Targeting wild-type Erythrocyte receptors for Plasmodium falciparum and vivax Merozoites by Zinc Finger Nucleases In- silico: Towards a Genetic Vaccine against Malaria
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Date
2012
Journal Title
Journal ISSN
Volume Title
Publisher
Genetic Vaccines and Therapy
Abstract
Malaria causes immense human morbidity and mortality globally. The plasmodium species vivax and falciparum cause over 75 % clinical malaria cases. Until now, gene-based strategies against malaria have only been applied to plasmodium species and their mosquito-vector. Merozoites of these two respective plasmodium species target and invade red blood cells (RBCs) by using the duffy antigen receptor for chemokines (DARC), and Sialic Acid (SLC4A1) residues of the O-linked glycans of Glycophorin A. RBCs of naturally selected duffy-negative blacks are resistant to P.vivax tropism. We hypothesized that artificial aberration of the host-pathway by target mutagenesis of either RBC –receptors, may abolish or reduce susceptibility of the host to malaria. As a first step towards the experimental actualization of these concepts, we aimed to identify zinc finger arrays (ZFAs) for constructing ZFNs that target genes of either wild-type host-RBC- receptors.
Description
Keywords
Malaria, Plasmodium, P. falciparum, P. vivax, Merozoites, RBC-receptors, Darc, Glycophorin A, Zinc finger nucleases, Host-pathway, Abrogation, Genetic vaccine
Citation
Kajumbula et al.: Targeting wild-type Erythrocyte receptors for Plasmodium falciparum and vivax Merozoites by Zinc Finger Nucleases In- silico: Towards a Genetic Vaccine against Malaria. Genetic Vaccines and Therapy 2012 10:8. doi:10.1186/1479-0556-10-8