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© 2001 SAGE Publications Synthetic Hammerhead Ribozymes as Tools in Gene ExpressionOral Research Laboratory, Faculty of Dentistry, University of Oslo, PO Box 1109, Blindern, N-0317 Oslo, Norway; spl{at}odont.uio.no The assessment of genetic controls for sequential developmental processes such as tooth formation and biomineralization is often difficult in transgenic "knockout" models, where phenotypes reflect only the permanent eradication of a gene, and reveal little about the dynamic range of expression for the gene(s) involved. One promising strategy to overcome this problem is through the use of ribozymes, a class of metalloenzymes made entirely of ribonucleic acid (RNA), that are capable of cleaving other RNA molecules in a catalytic fashion. Their activity can be targeted against specific mRNAs by selection of unique sequences flanking a conserved catalytic motif. In synthetic ribozymes, specificity, stability, and cell permeability can be dramatically improved by the incorporation of chemically modified ribonucleotides. This review focuses on the design and application of hammerhead ribozymes, the best-known and most widely used class of RNA-based enzymes. So far, except for a few conserved structures at the catalytic core, no one particular model or superior ribozyme design has been identified. It may well be that each cell, tissue, and organism has different requirements for the uptake, activity, and stability of hammerhead ribozymes. However, designed ribozymes can be highly effective agents for timed and localized elimination of gene products. As the 3D structures of active hammerhead molecules are revealed, more effective ribozymes will be developed. Today, developments in ribozyme-mediated sequence-specific blocking of gene expression hold great promise for active RNA enzymes as tools in biomolecular research and for eliminating unwanted gene expression in human diseases.
Key Words: Synthetic hammerhead ribozymes • ribozyme applications • ribozyme design • ribozyme delivery • ribozyme target selection.
Critical Reviews in Oral Biology & Medicine, Vol. 12, No. 6,
469-478 (2001) This article has been cited by other articles:
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