Neutralization of several adult and paediatric HIV-1 subtype C isolates using a shortened synthetic derivative of gp120 binding aptamer called UCLA1.

Abstract

This paper present a chemically synthesised derivative of the B40 parental aptamer, called UCLA1 (Cohen et al., 2008), was used for neutralization of endemic subtype C clinical isolates of HIV-1 from adult and paediatric patients and subtype B lab adapted strains. The UCLA1 RNA aptamer was used for neutralization of a panel of HIV-1 subtype C and HIV-1 subtype B Env-pseudotyped viruses. Neutralization of HIV-1 was measured in duplicate as a reduction in luciferase gene expression after a single-round infection of TZM-bl cells with the Env-pseudotyped viruses as previously described (Gray et al., 2006). The binding affinity and dissociation constant of the aptamer were measured against HIV-1 subtype C Du151 gp120 glycoprotein using the BIAcore Surface Plasmon Resonance Technology (SPR) technology. Cytotoxicity of the aptamer was measured overnight in TZM-bl cells using an ATP-based luminescent assay. The therapeutic index (TI) of the aptamer was determined at a CC50 of 500nM for all the viruses tested