New Compound Combining an Integrase-Targeting Aptamer and a Small Interfering RNA Targeting the Trans-Activation Response/Poly A Region of HIV-1 Potently Suppresses HIV-1 Replication

We have developed a novel aptamer-based siRNA delivery system for HIV therapy. Apsi510 was obtained by chemical conjugation of an anti-HIV integrase aptamer and an siRNA sequence targeting the HIV-1 TAR/poly A regions to a dendron [2-((4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)phenyl)amino)acetaldehyde]. Apsi510 activity against HIV-1NL4.3 was evaluated in two experimental systems using HeLa CD4+ and TZM-bl cells. Apsi510 activity was dose-dependent and inhibited >95% of viral replication at 50 nM. Apsi510 inhibited HIV-1 replication to a similar extent as siRNA alone, indicating efficient intracellular release of the siRNA molecule. Apsi510 is a promising drug candidate for the treatment and prevention of HIV.