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.
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This book gives a nearly complete overview of the current state-of-the-art oligonucleotide drugs. … provides valuable insights into the great opportunities that are presented by this technology.
—Dr. Kees Fluiter, The University of Amsterdam, in ChemMedChem, Vol. 4, 2009
This edition is a cutting edge document including up-to-date cited references and a variety of compelling clinical case studies, and it of course retains the superb basic principles and background to antisense drug technologies featured in the first edition.
—Gary Evans, Industrial Research Ltd., in Journal of Medicinal Chemistry, 2008, Vol. 51, No. 5
Mechanisms of Antisense Drug Action, an Introduction, S.T. Crooke, T. Vickers, Walt Lima, and H. Wu
The RNase H Mechanism, W. Lima, H. Wu, and S.T. Crooke
Small RNA Silencing Pathways, A. Sigova and P.D. Zamore
Splice Switching Oligonucleotides as Potential Therapeutics, P. Sazani, M.A. Graziewicz, and R. Kole
The Basics of Oligonucleotide-Based Therapeutics
Basic Principles of Antisense Drug Discovery, S.M. Freier and A.T. Watt
The Medicinal Chemistry of Oligonucleotides, E.E. Swayze and B. Bhat
Basic Principles of the Pharmacokinetics of Antisense Oligonucleotide Drugs, A.A. Levin, R.Z. Yu, and R.S. Geary
Routes and Formulations for Delivery of Antisense Oligonucleotides, G.E. Hardee, L.G. Tillman, and R.S. Geary
Liposomal Formulations for Nucleic Acid Delivery, I. MacLachlan
Hybridization-Based Drugs: Basic Properties 2 _ - O -Methoxyethyl Oligonucleotides
Pharmacological Properties of 2_- O-Methoxyethyl-Modified Oligonucleotides, C.F. Bennett
Pharmacokinetic/Pharmacodynamic Properties of Phosphorothioate 2_- O-(2-Methoxyethyl)-
Modified Antisense Oligonucleotides in Animals and Man, R.S. Geary, R.Z. Yu, A. Siwkowski, and A.A. Levin
Toxicologic Properties of 2_- O-Methoxyethyl Chimeric Antisense Inhibitors in Animals and Man, S.P. Henry, T.W. Kim, K. Kramer-Stickland, T.A. Zanardi, R.A. Fey, and A.A. Levin
An Overview of the Clinical Safety Experience of First- and Second-Generation Antisense Oligonucleotides, T.J. Kwoh
Manufacturing and Analytical Processes for 2_- O-(2-Methoxyethyl)-Modified Oligonucleotides, D.C. Capaldi and A.N. Scozzari
Hybridization-Based Drugs: Basic Properties Duplex RNA Drugs
Utilizing Chemistry to Harness RNA Interference Pathways for Therapeutics: Chemically Modified siRNAs and Antagomirs, M. Manoharan and K.G. Rajeev
Discovery and Development of RNAi Therapeutics, A.R. de Fougerolles and J.M. Maraganore
Other Chemical Classes of Drugs
Optimization of Second-Generation Antisense Drugs: Going Beyond Generation 2.0, B.P. Monia, R.Z. Yu, W. Lima, and A. Siwkowski
Modulating Gene Function with Peptide Nucleic Acids (PNA), P.E. Nielsen
Locked Nucleic Acid, T. Koch and H. Ørum
Morpholinos, P.L. Iversen
Potential Therapeutic Applications of Antisense Oligonucleotides in Ophthalmology, L.R. Grillone and S.P. Henry
Cardiovascular Therapeutic Applications, R. Crooke, B. Baker, and M. Wedel
Developing Antisense Drugs for Metabolic Diseases: A Novel Therapeutic Approach, S. Bhanot
Inflammatory Diseases, S.A. Gregory and J.G. Karras
Antisense Oligonucleotides for the Treatment of Cancer, B.A. Hadaschik and M.E. Gleave
Targeting Neurological Disorders with Antisense Oligonucleotides, R.A. Smith and T.M. Miller
Mechanisms and Therapeutic Applications of Immune Modulatory Oligodeoxynucleotide and Oligoribonucleotide Ligands for Toll-Like Receptors, J. Vollmer and A.M. Krieg
Aptamer Opportunities and Challenges, C. Wilson
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