Aptamer constructs and the Inhibition of HIV-1

Megan Breeden
University of Texas at Austin

The Human Immunodeficiency Virus (HIV-1) is a pathogen that is on the rise worldwide. It is estimated that 37 million adults and 2.5 million children were living with HIV in 2003. Treatments commonly used against HIV-1 cause harm not only to the virus, but also to the victim due to their toxicity. The fact that the virus frequently mutates also impedes the effectiveness of treatments.

Intramer therapy is a possible solution to the problems with the traditional treatment of HIV-1. Intramer therapy works through in the intracellular expression of nucleic acid molecules binding to specific HIV-1 target proteins. These nucleic acid molecules are generated through in vitro selection to tightly and specifically bind proteins or other ligands. Ideally, once the aptamers are expressed in the infected cell, they would bind to their corresponding HIV-1 protein and the protein would no longer be able to function.

The aptamers were generated for the following HIV-1 proteins: nuecleocapsid (nc) that functions to assemble the viral RNA into virons, reverse transcriptase (rt) that functions to reverse transcribe the viral RNA into DNA and finally, integrase (int) that functions to guide the insertion of viral RNA into the cell genome. The aptamers are the nc-aptamer, rt-aptamer, int-aptamer, (other anti-HIV-1 aptamers are available, but these are our aptamers of interest). Each of these proteins were separately used as targets to generate inhibitory aptamers. We have proposed the use of aptamers for intramer therapy and are now using aptamers to inhibit the effects of HIV-1.