Chadwick / Cardew Oligonucleotides as Therapeutic Agents

1. Auflage 2008
ISBN: 978-0-470-51540-2
Verlag: John Wiley & Sons
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 260 Seiten, E-Book

Reihe: Novartis Foundation Symposium

The use of oligonucleotides as therapeutic agents rests upon their ability to interfere, in a sequence-specific manner, with the fundamental machinery of protein synthesis either by binding to the mRNAs transcribed from a gene or by binding directly to a target gene. This approach can be used not only for inhibition of the synthesis of host proteins but also of those required by invading pathogens. Potential therapeutic applications are enormous, ranging over hypertension, cardiovascular disease, autoimmune disease, vital and other parasitic infections (especially HIV), and cancer. This book discusses the chemistry and pharmacokinetics of oligonucleotides and their analogues, and surveys the results of structure-activity studies and current clinical trials. It also critically reviews the problems with antisense therapy, such as the enzymatic destruction of oligonucleotides, the doses required for a therapeutic response, the difficulty in directing oligonucleotides to particular target tissues and cells, the need for parenteral administration, and doubts concerning the mechanism of action (especially problems associated with non-specific binding to proteins) and long-term effects.

Autoren/Hrsg.

Chadwick, Derek J.

Cardew, Gail

Inhaltsverzeichnis

Oligonucleotide Analogues: An Overview;
Phosphorothioate Oligodeoxynucleotides: Large Scale Synthesis andAnalysis, Impurity Characterization and the Effects of PhosphorousStereochemistry;
Discovering Antisense Reagents by Hybridization of RNA toOligonucleotide Arrays;
Pharmacokinetics of Oligonucleotides in Cell Culture;
Pharmacokinetics of Antisense Oligonucleotides;
Cellular Pharmacology of Antisense Oligodeoxynucleotides;
Sequence -Specific Control of Gene Expression by Antigene and ClampOligonucleotides;
Differential Oligonucleotide Activity in Cell Culture Versus MouseModels;
Structure-Activity Relationships in Cell Culture;
Progress in Antisense Therapeutics;
Treating Human Myelogenous Leukaemia With Oligonucleotides Targetedto the C-Myb Gene: Two Years Clinical Experience;
Therapeutic Applications of Catalytic Antisense RNAs;
Exogenous Application of Ribozymes for the Inhibition of GeneExpression;
SELEX Derived Drugs;
In Vivo Production of Oligonucleotide Applications for AntisenseDNA.