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Therapeutic Applications of Ribozymes
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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.
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Table of Contents

Small Efficient Hammerhead Ribozymes Philip Hendry, Trevor J. Lockett, and Maxine J. McCall The Hairpin Ribozyme: Discovery and Development for Gene Therapy Arnold Hampel Molecular Manipulations of the Catalytic RNAs from the Human Hepatitis Delta Virus N. Kyle Tanner The Design, Production, and Validation of an Anti-HIV Type 1 Ribozyme Lun-Quan Sun, Wayne Gerlach, and Geoff Symonds Methods for Treating HIV by Gene Therapy Using Ribozymes Eric M. Poeschla, Mang Yu, Mark C. Leavitt, and Flossie Wong-Staal An Expression Vector for Multiple Ribozymes Jun Ohkawa, Yutaka Takebe, and Kazunari Taira Viral RNA Targets for Ribozymes: Influenza A Virus Gerd Hobom and Annette Menke Hammerhead Ribozyme-Mediated Cleavage of Hepatitis B Virus RNA Fritz von Weizsacker, Hubert E. Blum, and Jack R. Wands Bovine Leukemia Virus Ribozymes Glenn H. Cantor Use of Ribozymes to Specifically Alter the MDR-1 Phenotype David Y. Bouffard Adenoviral-Mediated Anti-H-ras Ribozyme for the Treatment of Bladder Cancer Akira Irie, Jerry Tsai, and Mohammed Kashani-Sabet Tissue-Specific Delivery of an Anti-H-ras Ribozyme Against Malignant Melanoma Tsukasa Ohkawa and Mohammed Kashani-Sabet Ribozymes as a Novel Approach for the Treatment of Human Pancreatic Carcinoma Hiroshi Kijima, David Y. Bouffard, and Kevin J. Scanlon K-ras Ribozyme for Lung Cancer Alex W. Tong, Yu-An Zhang, John Nemunaitis, and Gabriele Mues Anti-c-erb-B-2 Ribozyme for Breast Cancer Toshiya Suzuki, Lisa D. Curcio, Jerry Tsai, and Mohammed Kashani-Sabet Ribozymes: Applications in Cancer Metastasis Research Gunhild M. Maelandsmo, Inge Kjonniksen, Eivind Hovig, Kevin J. Scanlon, and Oystein Fodstad Preformed Ribozymes: Strategies for Design and In Vivo Applicationas Anticytokine Agents Mouldy Sioud Folate-Polylysine-Mediated Delivery of a Multiunit Anti-BCR/ABL Ribozyme to BCR/ABL-Transformed 32D Cells Lance H. Leopold, Scott K. Shore, Ramana M. V. Reddy, and E. Premkumar Reddy Ribozymes Targeted Against AML1/MTG8: Evaluation of Ribozyme Efficiency in a Cell-Free System and Transfection with Cationic Liposome Hiromichi Matsushita, Hiroyuki Kobayashi, Masahiro Kizaki, and Yasuo Ikeda Ribozyme Targeting of the Growth Factor Pleiotrophin Frank Czubayko, Anke M. Schulte, and Anton Wellstein Ribozyme-Mediated Inhibition of Cell Proliferation: A Model for Identifying and Refining a Therapeutic Ribozyme Thale C. Jarvis, Dennis Macejak, and Larry Couture Inhibition of bAPP Synthesis by Ribozymes and Oligonucleotides in a Coupled Reticulocyte Transcription Translation System Marilyn Smedman and Robert B. Denman Selective Modification of Fatty Acid Synthesis Pathway by Expression of an Acetyl-CoA Carboxylase-Specific Ribozyme Gene Joohun Ha In Vivo Knockout of a Tissue-Specific Gene by Synthetic Ribozymes S. Petter Lyngstadaas, Brian S. Sproat, Martina Blaschke, Janos Ludwig, Thomas Rupp, and Hans P. Prydz Ribozyme-Mediated Downregulation of Gene Expression in Transgenic Mice Shimon Efrat Targeted Cleavage of RNA Using External Guide Sequences and Eukaryotic RNase P Yan Yuan and Fenyong Liu Application of In Vitro Selection in Design of External Guide Sequences That Direct Efficient Cleavage of RNA by RNase P Yan Yuan A PCR-Based Approach to Hammerhead Ribozyme Synthesis Katalin Kariko and Elliot S. Barnathan Measurement of Ribozyme Activity Using RNase Protection P. Kamath and E. J. Shillitoe Index

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". . . an impressive collection of ribozyme applications. . .a useful investment for anyone who contemplates or is actively using ribozymes for target RNA inactivations."-Nature Medicine

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