Development Of Aptamer-based HIV-1 Entry Inhibitor Prophylactic Drug | 9212
Journal of Clinical & Experimental Pathology
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AIDS remains a major public health problem globally, especially in Southern Africa where over 6.4 million people are infected
by the most prevalent HIV-1 subtype C. To help stop the spread of HIV-1 subtype C, we isolated 2ʹ-F-RNA aptamers against
gp120, with a view of developing them as entry inhibitor drugs. In this study, we evaluated the neutralization activity of two
aptamers (CSIR1.1 and UCLA1) against HIV-1 subtype C, their toxicity effects and mapped their epitopes on gp120. UCLA1 and
CSIR1.1 were tested against a 32 Env pseudotyped panel from HIV-1 subtype C. In addition, UCLA1 was further tested against
10 clinical isolates in PBMC and MDM. We evaluated the cytotoxic effects of aptamers in target cells using ATP and PMTS
proliferation assay and mapped their epitopes on gp120 by site directed mutagenesis. UCLA1 and CSIR1.1 neutralized infectivity
of 79 % and 84 % pseudotyped viruses, respectively. UCLA1, further inhibited more than 60 % of clinical isolates. We noted that,
aptamers neutralized both R5 and X4 tropic viruses with mean IC
value of 10 nM and did not affect cell viability after 72 hrs
incubation with a concentration of 500 nM. The mapping studies revealed that CSIR1.1 and UCLA1 bind to conserved region of
V1/V2 region and V3 loop on gp120. Our results showed that RNA aptamers prevent infection of HIV-1 subtype C by binding to
conserved regions on gp120, without toxicity effects. This warrant further studies to develop RNA aptamer as prophylactic drugs
to prevent infection of HIV-1 subtype C.
Grace, recently submitted her Ph.D. for evaluation at University of Cape Town collaboration with CSIR (Council for Scientific and Industrial Research).
She completed part of her Ph.D. at Scripps Research Institute after being awarded the Fogarty global scholarship and recently won a clinical
excellence awards at the 6
South African AIDS conference.
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