Hammerhead ribozymes for target validation
- 1 April 2002
- journal article
- review article
- Published by Informa Healthcare in Emerging Therapeutic Targets
- Vol. 6 (2) , 235-247
- https://doi.org/10.1517/14728222.6.2.235
Abstract
Expensive failures in the pharmaceutical industry might be avoided by target validation at an early stage. Often, the full consequences of inhibiting a chosen drug target do not emerge until late in the development process. One option is to use hammerhead ribozymes as highly specific ribonucleases targeted exclusively at the mRNA encoding the target protein. The first part of this review is concerned with the mechanism and design of hammerhead ribozymes. This includes the chemistry of their action, specificity of cleavage and ability to discriminate between different mRNAs and selection of suitable cleavage sites. In considering their use for target validation, hammerhead ribozymes are divided into two categories. Endogenous ribozymes are transcribed inside the cell where they act whilst exogenous are introduced into the cell from outside. Exogenous ribozymes are synthesised chemically and must be protected against cellular nucleases. Information is provided on transfection methods and vectors that have b...Keywords
This publication has 88 references indexed in Scilit:
- Hammerhead Ribozyme as a Therapeutic Agent for Hyperlipidemia: Production of Truncated Apolipoprotein B and Hypolipidemic Effects in a Dyslipidemia Murine ModelHuman Gene Therapy, 2000
- Ribozyme to Human TGF-β1 mRNA Inhibits the Proliferation of Human Vascular Smooth Muscle CellsBiochemical and Biophysical Research Communications, 2000
- Hammerhead Ribozyme Specifically Inhibits Mutant K-ras mRNA of Human Pancreatic Cancer CellsBiochemical and Biophysical Research Communications, 1998
- Hammerhead Ribozymes against γ-Glutamylcysteine Synthetase mRNA Down-Regulate Intracellular Glutathione Concentration of Mouse Islet CellsBiochemical and Biophysical Research Communications, 1998
- Ribozyme Targeting of Receptor for Advanced Glycation End Products in Mouse Mesangial CellsBiochemical and Biophysical Research Communications, 1998
- Ex VivoEffects Associated with the Expression of abcr-abl-Speciftc Ribozyme in a CML Cell LineAntisense and Nucleic Acid Drug Development, 1998
- Ribozyme modulation of lipopolysaccharide‐induced tumor necrosis factor‐α production by peritoneal cells in vitro and in vivoEuropean Journal of Immunology, 1996
- Ribozymes Cleave the AML1/MTG8 Fusion Transcript and Inhibit Proliferation of Leukemic Cells with t (8;21)Biochemical and Biophysical Research Communications, 1995
- Functional Characterization of Ribozymes Expressed Using U1 and T7 Vectors for the Intracellular Cleavage of ANF mRNABiochemistry, 1994
- Ribozyme Targeting of HIV-1 LTRBiochemical and Biophysical Research Communications, 1994