title: Aptamer-siRNA chimeras for HIV.
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.
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, 1500 E Duarte Rd., Duarte, CA, 91010, USA, mtakahashi@coh.org.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.forename: John J
authors.initials: JJ
authors.lastname: Rossi
mesh_terms: D000818:Animals; D052158:Aptamers, Peptide / Q000235:genetics*; D015704:CD4 Antigens / Q000235:genetics; D004274:DNA, Recombinant / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics*
chemical_list: D052158:Aptamers, Peptide; D015704:CD4 Antigens; D004274:DNA, Recombinant; D015699:HIV Envelope Protein gp120; D034741:RNA, Small Interfering