Aptamer-siRNA chimeras for HIV

Advances in Experimental Medicine and Biology
Mayumi TakahashiJohn J Rossi

Abstract

Since 1980s, HIV/AIDS has escalated into a global pandemic. Although combinatorial antiretroviral therapy (cART) regimens can suppress plasma virus levels to below the detection limit and the survival rate of HIV-1 infected patients has been improving, long-term cART holds the potential to cause a number of chronic diseases. RNA interference (RNAi) is considered as a powerful method for developing new generation of therapeutics. Discovery of small interfering RNAs (siRNAs) shed light on limitations of targets that are "undruggable" with current technologies. However, delivery remains a major hurdle of siRNA-based therapy. Recent progress in technology of engineering nucleic acid enables a targeted delivery of siRNAs using aptamers, which, as often regarded as nucleic acid "antibodies," can recognize/bind to multiple different proteins and small-molecule targets by forming scaffolds for molecular interactions. SELEX technology enabled to isolate highly target specific aptamers from a random sequence oligonucleotide library. A number of aptamers for HIV-1 proteins as well as host proteins that interact with HIV-1 have been developed and some of them have potent viral neutralization ability and inhibition of HIV-1 infectivity. The...Continue Reading

Citations

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