Antisense Research and Application

Antisense technology may result in dramatic changes in the therapy of many diseases and may provide tools to dissect pharmacological processes and to confirm the roles of various genes. In this volume, progress in the understanding of antisense technology and its use in creating new drugs is discussed. Potential caveats, pitfalls and limitations of the technology are also presented. In the next few years the pace at which new molecular targets will be identified will increase exponentially as the sequencing of the human genome and of other genomes proceeds.

1 Basic Principles of Antisense Therapeutics.- 2 Antisense Medicinal Chemistry.- 3 In Vitro Cellular Uptake, Distribution, and Metabolism of Oligonucleotides.- 4 Pharmacokinetic Properties of Phosphorothioates in Animals – Absorption, Distribution, Metabolism and Elimination.- 5 Toxicity of Oligodeoxynucleotide Therapeutic Agents.- 6 Pharmacokinetic Properties of Phosphorothioate Oligonucleotides in Immune Stimulation by Oligonucleotides in Humans.- 7 Safety and Tolerance of Phosphorothioates in Humans.- 8 Inmune Stimulation by Oligonucleotides.- 9 Pharmacological Inhibition of Dopaminergic and Other Neurotransmitter Receptors Using Antisense Oligodeoxynucleotides.- 10 Pharmacological Effects of Antisense Oligonucleotide Inhibition of Immediate-Early Response Genes in the CNS.- 11 Inhibition of G Proteins by Antisense Drugs.- 12 Use of Antisense Oligonucleotides to Modify Inflammatory Processes.- 13 Antisense Oligonucleotides and Their Anticancer Activities.- 14 Pharmacological Activity of Antisense Oligonucleotides in Animal Models of Disease.- 15 Clincial Antiviral Activities.- 16 Antisense Oligonucleotides to Protein Kinase C-a and C-raf Kinase: Rationale and Clinical Experience in Patients with Solid Tumors.- 17 Nucleic Acid Therapeutics for Human Leukemia: Development and Early Clinical Experience with Oligodeoxynucleotides Directed at c-myb.- 18 Properties of ISIS 2302, an Inhibitor of Intercellular Adhesion Molecule-1, Humans.- 19 Pharmacokinetics and Bioavailability of Antisense Oligonucleotides Following Oral and Colorectal Administrations in Experimental Animals.- 20 Antisense Properties of Peptide Nucleic Acid.- 21 Triple Helix Strategies and Progress.