This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite the dramatic success of highly active antiretroviral therapy (HAART) in inhibiting viral replication in HIV-infected subjects, it is increasingly clear that there is a compelling rationale for the development of complementary therapies, most notably genetic therapies for HIV disease. Recent experiments have demonstrated quite potent inhibition of HIV-1 and RT-SHIV replication by RT-specific aptamers. Aptamers have a number of distinctive advantages as a modality to inhibit HIV replication, including the ability to target multiple elements of the retroviral life cycle, their relative resistance to the emergence of escape viruses, and their observed potency in inhibiting HIV replication. Following transduction of cell lines with retroviral vectors expressing aptamers specific for HIV-1, we observed significant inhibition of SHIV RT replication. Stable retroviral producer cell lines expressing aptamers have been generated and used to transduce transformed cell lines. These studies should yield important information regarding the efficacy and safety of aptamer-based stem cell gene therapy for AIDS and ultimately facilitate the development of similar trials in HIV-infected people.
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