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.

Features:

• Presents the logarithmic progress of oligonucleotide-based therapeutics, particularly antisense therapeutics
• Interprets recent pharmaceutical technology set backs within the context successful advancements in the field
• Examines new chemistries and mechanisms including 2' methoxyethyl chimeras and duplex RNA
• Illustrates concepts with numerous tables, as well as black and white illustrations and color figures
• Features contributions from leaders in the field

Part 1 gives an 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.

Part 2demonstrate the basics of oligonucleotide therapeutics by delineating medicinal chemistry, pharmacokinetics, and delivery routes such as liposomal formulations for nucleic acid delivery.

Part 3 details hybridization based drugs and considers the dramatic advances represented by 2' methoxyethyl chimeric antisense inhibitors and duplex RNA drugs.

Part 4 describes other chemical classes of drugs and mechanisms of action with further discussions on improving the second generation antisense drugs.

Part 5 delves deeply into therapeutic applications and examines the potential of antisense drugs for the alleviation of cardiovascular diseases, metabolic diseases, inflammatory diseases, cancer, neurological disorders, and immune modulation.

Contents

Introduction

1. Mechanisms of Antisense Drug Action, an Introduction
2. The RNase H Mechanism
3. Small RNA Silencing Pathways
4. Splice Switching Oligonucleotides as Potential Therapeutics

The Basics of Oligonucleotide-Based Therapeutics

5. Basic Principles of Antisense Drug Discovery
6. The Medicinal Chemistry of Oligonucleotides
7. Basic Principles of the Pharmacokinetics of Antisense Oligonucleotide Drugs
8. Routes and Formulations for Delivery of Antisense Oligonucleotides
9. Liposomal Formulations for Nucleic Acid Delivery

Hybridization-Based Drugs: Basic Properties 2_-O-Methoxyethyl Oligonucleotides

10. Pharmacological Properties of 2_-O-Methoxyethyl-Modified Oligonucleotides
11. Pharmacokinetic/Pharmacodynamic Properties of Phosphorothioate 2_-O-(2-Methoxyethyl)- Modified Antisense Oligonucleotides in Animals and Man
12. Toxicologic Properties of 2_-O-Methoxyethyl Chimeric Antisense Inhibitors in Animals and Man
13. An Overview of the Clinical Safety Experience of First- and Second-Generation Antisense Oligonucleotides
14. Manufacturing and Analytical Processes for 2_-O-(2-Methoxyethyl)-Modified Oligonucleotides

Hybridization-Based Drugs: Basic Properties Duplex RNA Drugs

15. Utilizing Chemistry to Harness RNA Interference Pathways for Therapeutics: Chemically Modified siRNAs and Antagomirs
16. Discovery and Development of RNAi Therapeutics

Other Chemical Classes of Drugs

17. Optimization of Second-Generation Antisense Drugs: Going Beyond Generation 2.0
18. Modulating Gene Function with Peptide Nucleic Acids (PNA)
19. Locked Nucleic Acid
20. Morpholinos

Therapeutic Applications

21. Potential Therapeutic Applications of Antisense Oligonucleotides in Ophthalmology
22. Cardiovascular Therapeutic Applications
23. Developing Antisense Drugs for Metabolic Diseases: A Novel Therapeutic Approach
24. Inflammatory Diseases
25. Antisense Oligonucleotides for the Treatment of Cancer
26. Targeting Neurological Disorders with Antisense Oligonucleotides
27. Mechanisms and Therapeutic Applications of Immune Modulatory Oligodeoxynucleotide and Oligoribonucleotide Ligands for Toll-Like Receptors
28. Aptamer Opportunities and Challenges

Index

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