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Full Description
The purpose of Applications Therapeutic of Ribozymes is to provide an overview of the utility of ribozymes to selectively inhibit the expression of RNA. The ribozyme applications appearing in this book should benefit not only those experienced in ribozymes, but also those applying this ribozyme technology for the first time. It is hoped that a better understanding of the therapeutic application ofribozymes will have a significant impact on human disease in the near future. The field ofribozyme biochemistry has come a long way since the initial observation that RNA is capable of catalysis, initially in cis during processing of larger molecules and ultimately the use of ribozymes in trans to achieve cleavage of target sequence. The fundamental observation that hammerhead (and subsequently hairpin) ribozymes could be designed to cleave a target messenger RNA, and the clarification of sequence restrictions in both the ribozyme and the target RNA, have paved the ways for the use of ribozymes as a tool to manipulate gene expression at the molecular level. This had pre- ously been a domain of antisense oligonucleotides and triplex DNA. Sub- quent studies have explored the myriad biological systems in which ribozyme-mediated inhibition of genes involved in various cellular processes may be used to uncouple important signaling pathways or to reverse the p- notypic expression of a pathologic process.
Contents
Small Efficient Hammerhead Ribozymes.- The Hairpin Ribozyme.- Molecular Manipulations of the Catalytic RNAs from the Human Hepatitis Delta Virus.- The Design, Production, and Validation of an Anti-HIV Type 1 Ribozyme.- Methods for Treating HIV by Gene Therapy Using Ribozymes.- An Expression Vector for Multiple Ribozymes.- Viral RNA Targets for Ribozymes.- Hammerhead Ribozyme-Mediated Cleavage of Hepatitis B Virus RNA.- Bovine Leukemia Virus Ribozymes.- Use of Ribozymes to Specifically Alter the MDR-1 Phenotype.- Adenoviral-Mediated Anti-H-ras Ribozyme for the Treatment of Bladder Cancer.- Tissue-Specific Delivery of an anti-H-ras Ribozyme Against Malignant Melanoma.- Ribozymes as a Novel Approach for the Treatment of Human Pancreatic carcinoma.- K-rasRibozyme for Lung Cancer.- Anti-c-erb-B-2 Ribozyme for Breast Cancer.- Ribozymes.- Preformed Ribozymes.- Folate-Polylysine-Mediated Delivery of a Multiunit Anti-BCR/ABL Ribozyme to BCR/ABL-Transformed 32D Cells.- Ribozymes Targeted Against AML1/MTG8.- Ribozyme Targeting of the Growth Factor Pleiotrophin.- Ribozyme-Mediated Inhibition of Cell Proliferation.- Inhibition of ?APP Synthesis by Ribozymes and Oligonucleotides in a Coupled Reticulocyte Transcription Translation System.- Selective Modification of Fatty Acid Synthesis Pathway by Expression of an Acetyl-CoA Carboxylase-Specific Ribozyme Gene.- In Vivo Knockout of a Tissue-Specific Gene by Synthetic Ribozymes.- Ribozyme-Mediated Downregulation of Gene Expression in Transgenic Mice.- Targeted Cleavage of RNA Using External Guide Sequences and Eukaryotic RNase P.- Application of In Vitro Selection in Design of External Guide Sequences That Direct Efficient Cleavage of RNA by RNase P.- A PCR-Based Approach to Hammerhead Ribozyme Synthesis.- Measurement of RibozymeActivity Using RNase Protection.
