Selection of RNA aptamers that inhibit mutant 3 HIV-1 reverse transcriptase

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Selection of RNA aptamers that inhibit mutant 3 HIV-1 reverse transcriptase

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Title: Selection of RNA aptamers that inhibit mutant 3 HIV-1 reverse transcriptase
Author: Husain, Naeem
Abstract: Acquired immunodeficiency syndrome (AIDS) is one of the most widespread diseases on the planet, and the need for new forms of treatment has become paramount. Even though there are treatments against human immunodeficiency virus (HIV), the virus mutates readily and becomes resistant to these drugs. A mutation is a slight change in the virus that allows it to evade the action of the medication. Because resistance to anti-viral drugs is pervasive, it is imperative to find new ways to treat such mutant viruses. A promising field for the treatment of HIV is the application of aptamers. Aptamers are nucleic acids that form tertiary structures, which can bind to proteins tightly and selectively. If an aptamer bound and inhibited a key enzyme in the virus, it could help prevent the spread of HIV in the human body. An important target for therapeutics has been reverse transcriptase, which is vital for viral reproduction. Although aptamers that inhibit reverse transcriptase (RT) activity have already been isolated, these are against wild type HIV, or most common form of the virus. Thus, it is important to select for alternative aptamers that will inhibit other drug resistant forms of the virus. The Stanford University HIV drug resistant database lists twelve common drug resistant HIV variants with mutant forms of RT. The object of this study was to select a few aptamers that inhibited the activity of mutant clone 3 RT from the aforementioned database. Aptamers were found not only to prevent enzymatic action of RT, but also bound to other regions of the protein itself. This led to the testing of innovative techniques within the realm of aptamers by creating complexes that link two aptamers together, which can bind more tightly to the enzyme because there are more contact points between the aptamers and protein target. These findings also open the door to improving current aptamer microarray assay technology. Microarrays utilize aptamers that are placed on slides to detect the presence of a certain protein. The improvement comes from using aptamers, instead of antibodies (another molecule that binds to proteins) as the signal molecule for the test. Thus, aptamers can be used for both therapeutic and detection means against HIV.
Department: Biochemistry
Subject: College of Natural Sciences HIV human immunodeficiency virus aptamers reverse transcriptase
URI: http://hdl.handle.net/2152/13414
Date: 2010

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