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Science 9 March 1990:
Vol. 247. no. 4947, pp. 1222 - 1225
DOI: 10.1126/science.2107573
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Articles
Science, Vol 247, Issue 4947, 1222-1225
Copyright © 1990 by American Association for the Advancement of Science
Ribozymes as potential anti-HIV-1 therapeutic agents
N Sarver,
EM Cantin,
PS Chang,
JA Zaia,
PA Ladne,
DA Stephens,
and
JJ Rossi
Division of Research and Development Program, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Certain RNA molecules, called ribozymes, possess enzymatic, self-cleaving activity. The cleavage reaction is catalytic and no energy source is required. Ribozymes of the "hammerhead" motif were identified in plant RNA pathogens. These ribozymes possess unique secondary (and possibly tertiary) structures critical for their cleavage ability. The present study shows precise cleavage of human immunodeficiency virus type 1 (HIV-1) sequences in a cell-free system by hammerhead ribozymes. In addition to the cell-free studies, human cells stably expressing a hammerhead ribozyme targeted to HIV-1 gag transcripts have been constructed. When these cells were challenged with HIV-1, a substantial reduction in the level of HIV-1 gag RNA relative to that in nonribozyme-expressing cells, was observed. The reduction in gag RNA was reflected in a reduction in antigen p24 levels. These results suggest the feasibility of developing ribozymes as therapeutic agents against human pathogens such as HIV-1.
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