[Frontiers in Bioscience 11, 89-112, January 1, 2006]
HIV-1 inactivation by nucleic acid aptamers
Daniel M. Held 1, 3, Jay D. Kissel 1, James T. Patterson 2, David G. Nickens 2 and Donald H. Burke 2, 3
Departments of 1 Biology and 2 Chemistry, Indiana University, Bloomington, IN 47405, 3 Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212
TABLE OF CONTENTS
Although developments in small-molecule therapeutics for HIV-1 have been dramatic in recent years, the rapid selection of drug-resistant viral strains and the adverse side effects associated with long-term exposure to current treatments propel continued exploration of alternative anti-HIV-1 agents. Non-coding nucleic acids have emerged as potent inhibitors that dramatically suppress viral function both in vitro and in cell culture. In particular, RNA and DNA aptamers inhibit HIV-1 function by directly interfering with essential proteins at critical stages in the viral replication cycle (Figure 1). Their antiviral efficacy is expected to be a function, in part, of the biochemical properties of the aptamer-target interaction.
Accordingly, we present an overview of biochemical and cell culture analyses of the expanding list of aptamers targeting HIV-1. Our discussion focuses on the inhibition of viral enzymes (reverse transcription, proteolytic processing, and chromosomal integration), viral expression (Rev/RRE and Tat/TAR), viral packaging (p55Gag, matrix and nucleocapsid), and viral entry (gp120) (Table 1). Additional nucleic acid-based strategies for inactivation of HIV-1 function (including RNAi, antisense, and ribozymes) have also demonstrated their utility. These approaches are reviewed in other chapters of this volume and elsewhere (1-5).