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[General Articles] Ribozyme-Based Gene-Inactivation Systems Require A Fine Comprehension of their Substrate Specificities; the Case of Delta Ribozyme

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Abstract:

The ability of ribozymes (i.e. RNA enzymes) to specifically recognize and subsequently catalyze the cleavage of an RNA substrate makes them attractive for the development of therapeutic tools for the inactivation of both viral RNAs and mRNAs associated with various diseases. Several applicable ribozyme models have been tested both in vitro and in a cellular environment, and have shown significant promise. However, several hurdles remain to be surpassed before we generate a useful geneinactivation system based on a ribozyme. Among the most important requirements for further progress are a better understanding of the features that contribute to defining the substrate specificity for cleavage by a ribozyme, and the identification of the potential cleavage sites in a given target RNA. The goal of this review is to illustrate the importance of both of these factors at the RNA level in the development of any type of ribozyme based gene-therapy. This is achieved by reviewing the recent progress in both the structure-function relationships and the development of a gene-inactivation system of a model ribozyme, specifically delta ribozyme.

Keywords: gene-inactivation; hepatitis delta virus; ribozyme; rna structure-function; substrate specificity

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867033456486

Affiliations: RNA Group / Groupe ARN, Departement de Biochimie, Faculte de medecine, Universite de Sherbrooke, Sherbrooke, Quebec, J1H 5N4, Canada.

Publication date: December 1, 2003

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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