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Ribozyme-Mediated Inhibition of Cell Proliferation: A Model for Identifying and Refining a Therapeutic Ribozyme

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The discovery of enzymatic RNA molecules, termed ribozymes (1 ,2 ), fundamentally changed our view of the function of RNA in chemistry, biology, and medicine. Naturally occurring enzymatic RNA molecules catalyze sequence-specific RNA processing. The sequence specificity is determined by the ability of the ribozyme to base pair with nucleotides near the cleavage site of the target RNA; by altering the substrate recognition sequences, intramolecular, cis -cleaving ribozymes can be engineered to cleave in trans (reviewed in Cech, T. R., [3 ]). In theory, ribozymes can be engineered to cleave any RNA species, site-specifically, in the background of cellular RNA. This cleavage event renders the target mRNA unstable and abrogates protein expression.
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