Chapter title |
Aptamer-siRNA Chimeras for HIV.
|
---|---|
Chapter number | 11 |
Book title |
Gene Therapy for HIV and Chronic Infections
|
Published in |
Advances in experimental medicine and biology, January 2015
|
DOI | 10.1007/978-1-4939-2432-5_11 |
Pubmed ID | |
Book ISBNs |
978-1-4939-2431-8, 978-1-4939-2432-5
|
Authors |
Mayumi Takahashi, John C Burnett, John J Rossi, John C. Burnett, John 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 availability of these aptamers has given an idea of using aptamers for targeting delivery of siRNAs. So far, aptamers against either HIV-1 gp120 or CD4 have been eagerly evaluated as the aptamer portion of the aptamer-siRNA chimeras for the treatment or prevention of HIV-1. In this chapter, we highlight the development and therapeutic potential of aptamer-siRNA chimeras for HIV-1. |
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