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【电子书】Antisense Drug Technology
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Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition By Stanley T. Crooke Publisher: CRC Number Of Pages: 848 Publication Date: 2007-07-25 ISBN / ASIN: 0849387965 EAN: 9780849387968 Book Description: Extensively revised and updated, Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition reflects the logarithmic progress made in the past four years of oligonucleotide-based therapies, and, in particular, antisense therapeutics and research. Interpreting lessons learned from the clinical trials of first generation drugs, the book evaluates the technology as a whole and offers new directions and avenues of research and development. Divided into five parts, the book begins with a thorough introduction to the mechanism of antisense drug action including the RNase H mechanism, small RNA silencing pathways, and the potential therapeutics of splice switching oligonucleotides. Leading researchers demonstrate the basics of oligonucleotide therapeutics in part two by delineating medicinal chemistry, pharmacokinetics, and delivery routes such as liposomal formulations for nucleic acid delivery. Part three details hybridization based drugs and considers the dramatic advances represented by 2' methoxyethyl chimeric antisense inhibitors and duplex RNA drugs. Other chemical classes of drugs and mechanisms of action are described in part four with further discussions on improving the second generation antisense drugs. The final part delves deeply into therapeutic applications. Contributing authors examine the potential of antisense drugs for the alleviation of cardiovascular diseases, metabolic diseases, inflammatory diseases, cancer, neurological disorders, and immune modulation. Presenting a highly detailed, lucid discussion of the remarkable advances in the field, Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition provides the platform for researchers to continue to aggressively pursue the great opportunity represented by this exciting technology. Preface .............................................................................................................................................ix Acknowledgments...........................................................................................................................xi The Editor.....................................................................................................................................xiii Contributors...................................................................................................................................xv Part I Introduction .......................................................................................................................................1 Chapter 1 Mechanisms of Antisense Drug Action, an Introduction...................................................................3 Stanley T. Crooke, Timothy Vickers,Walt Lima, and Hongjiang Wu Chapter 2 The RNase H Mechanism ................................................................................................................47 Walt Lima, Hongjiang Wu, and Stanley T. Crooke Chapter 3 Small RNA Silencing Pathways.......................................................................................................75 Alla Sigova and Phillip D. Zamore Chapter 4 Splice Switching Oligonucleotides as Potential Therapeutics.........................................................89 Peter Sazani, Maria A. Graziewicz, and Ryszard Kole Part II The Basics of Oligonucleotide-Based Therapeutics ......................................................................115 Chapter 5 Basic Principles of Antisense Drug Discovery ..............................................................................117 Susan M. Freier and Andrew T. Watt Chapter 6 The Medicinal Chemistry of Oligonucleotides..............................................................................143 Eric E. Swayze and Balkrishen Bhat Chapter 7 Basic Principles of the Pharmacokinetics of Antisense Oligonucleotide Drugs ...........................183 Arthur A. Levin, Rosie Z. Yu, and Richard S. Geary Chapter 8 Routes and Formulations for Delivery of Antisense Oligonucleotides .........................................217 Gregory E. Hardee, Lloyd G. Tillman, and Richard S. Geary Chapter 9 Liposomal Formulations for Nucleic Acid Delivery......................................................................237 Ian MacLachlan Part III A Hybridization-Based Drugs: Basic Properties 2-O-Methoxyethyl Oligonucleotides ..................271 Chapter 10 Pharmacological Properties of 2-O-Methoxyethyl-Modified Oligonucleotides ..........................273 C. Frank Bennett Chapter 11 Pharmacokinetic/Pharmacodynamic Properties of Phosphorothioate 2-O-(2-Methoxyethyl)- Modified Antisense Oligonucleotides in Animals and Man .........................................................305 Richard S. Geary, Rosie Z. Yu, Andrew Siwkowski, and Arthur A. Levin Chapter 12 Toxicologic Properties of 2-O-Methoxyethyl Chimeric Antisense Inhibitors in Animals and Man .......................................................................................................................327 Scott P. Henry, Tae-Won Kim, Kimberly Kramer-Stickland, Thomas A. Zanardi, Robert A. Fey, and Arthur A. Levin Chapter 13 An Overview of the Clinical Safety Experience of First- and Second-Generation Antisense Oligonucleotides............................................................................................................365 T. Jesse Kwoh Chapter 14 Manufacturing and Analytical Processes for 2-O-(2-Methoxyethyl)-Modified Oligonucleotides............................................................................................................................401 Daniel C. Capaldi and Anthony N. Scozzari Part III B Hybridization-Based Drugs: Basic Properties Duplex RNA Drugs ..............................................435 Chapter 15 Utilizing Chemistry to Harness RNA Interference Pathways for Therapeutics: Chemically Modified siRNAs and Antagomirs .............................................................................437 Muthiah Manoharan and Kallanthottathil G. Rajeev Chapter 16 Discovery and Development of RNAi Therapeutics......................................................................465 Antonin R. de Fougerolles and John M. Maraganore Part IV Other Chemical Classes of Drugs ..................................................................................................485 Chapter 17 Optimization of Second-Generation Antisense Drugs: Going Beyond Generation 2.0 ................487 Brett P. Monia, Rosie Z. Yu,Walt Lima, and Andrew Siwkowski Chapter 18 Modulating Gene Function with Peptide Nucleic Acids (PNA)....................................................507 Peter E. Nielsen Chapter 19 Locked Nucleic Acid......................................................................................................................519 Troels Koch and Henrik Ørum Chapter 20 Morpholinos ..................................................................................................................................565 Patrick L. Iversen Part V Therapeutic Applications ...............................................................................................................583 Chapter 21 Potential Therapeutic Applications of Antisense Oligonucleotides in Ophthalmology ................585 Lisa R. Grillone and Scott P. Henry Chapter 22 Cardiovascular Therapeutic Applications ......................................................................................601 Rosanne Crooke, Brenda Baker, and Mark Wedel Chapter 23 Developing Antisense Drugs for Metabolic Diseases: A Novel Therapeutic Approach ...............641 Sanjay Bhanot Chapter 24 Inflammatory Diseases...................................................................................................................665 Susan A. Gregory and James G. Karras Chapter 25 Antisense Oligonucleotides for the Treatment of Cancer..............................................................699 Boris A. Hadaschik and Martin E. Gleave Chapter 26 Targeting Neurological Disorders with Antisense Oligonucleotides.............................................721 Richard A. Smith and Timothy M. Miller Chapter 27 Mechanisms and Therapeutic Applications of Immune Modulatory Oligodeoxynucleotide and Oligoribonucleotide Ligands for Toll-Like Receptors ............................................................747 Jörg Vollmer and Arthur M. Krieg Chapter 28 Aptamer Opportunities and Challenges .........................................................................................773 Charles Wilson Index..............................................................................................................................................801 http://media.imhb.cn/myspace/download.aspx?MSAutoID=63471&huid=460586 |
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