Design and cloning of an anti-HIV-1 Tat hammerhead ribozyme. (Withdrawn).

The Human Immunodeficiency Virus (HIV-1) is a retrovirus that is the causative agent of the Acquired Immune Deficiency Syndrome (AIDS). Since the beginning of the AIDS pandemic, some 30 million individuals worldwide have been affected resulting in greater than 12 million deaths. HIV-1 principally infects and destroys CD4+ T Helper Lymphocytes, which are responsible for overall control of the immune system. Current AIDS treatments are aimed at slowing the progression of the disease and are not curative. We are currently studying the use of anti-HIV ribozymes as a means of inhibiting viral replication. Ribozymes, in particular hammerhead ribozymes, are small catalytic RNAs that specifically cleave phosphodiester bonds of single-stranded target RNAs. We are currently studying the use of these reagents to inhibit the function of the HIV-1 Tat gene. Tat encodes a small protein that is responsible for the regulation of viral transcription and is therefore critical to viral replication. We have identified 18 sequences with Tat mRNA that are potential target sites for hammerhead-ribozyme mediated cleavage. The design and cloning of an anti-tat hammerhead ribozyme targeted to one of these sites, a GUC sequence, located at nucleotide 5877 of the HIV-1 genomic clone NL43 is described.

M. Leigh Stone-Ryan, William H. Jackson
Department of Biology and Geology
University of South Carolina