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Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition, 2nd Edition (Hardback) book cover

Antisense Drug Technology

Principles, Strategies, and Applications, Second Edition, 2nd Edition

Edited by Stanley T. Crooke

CRC Press

848 pages | 13 Color Illus. | 243 B/W Illus.

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Hardback: 9780849387968
pub: 2007-07-25
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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.

Reviews

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

Table of Contents

Introduction

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

Therapeutic Applications

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

Index

Subject Categories

    BISAC Subject Codes/Headings:
    MED009000
    MEDICAL / Biotechnology
    MED072000
    MEDICAL / Pharmacy
    SCI013000
    SCIENCE / Chemistry / General