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Pharmaceutical Aspects of Oligonucleotides

ISBN-10: 074840841X

ISBN-13: 9780748408412

Edition: 1999

Authors: Patrick Couvreur, Claude Malvy

List price: $265.00
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Description:

Oligonucleotides with base sequences complementary (antisense) to a specific RNA or DNA offer the exciting potential of selectively modulating the expression of an individual gene. Those molecules are gaining interest of the rapid progress in molecular biology and broad scope of potential applications in treating human diseases. However, oligonucleotides diffuse poorly through the biological barriers, including cell membrane. In addition, they are rapidly degraded in vivo by nucleases. Thus, to improve the administration of these compounds is a real challenge that this book will, in part, focus on. Therefore, particular emphasis will be placed on the developments of the chemistry as well as on the formulation and the controlled delivery of these compounds. Background information concerning intracellular trafficking and tissue distribution/pharmacokinetics will also be given. In addition, the therapeutical aspects will also be given consideration.The target audience are researchers working within academia and industry as well as those in management positions in companies that are involved in the field of oligonucleotide therapy. This book is also vital for postgraduate students who need to be well informed about this currently hot topic.
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Book details

List price: $265.00
Copyright year: 1999
Publisher: CRC Press LLC
Publication date: 12/16/1999
Binding: Hardcover
Pages: 336
Size: 7.00" wide x 9.50" long x 1.00" tall
Weight: 1.936

Contributors
Preface
General Features
Mechanisms of Action of Antisense Oligonucleotides
Introduction
Cell Proliferation Arrest through Release of Deoxynucleosides
Extracellular Aptameric Effects of Phosphorothioate Oligodeoxynucleotide Analogues
Aptameric Effects of G-quartet Oligonucleotides and Analogues
Immune Stimulation by Oligodeoxynucleotides Containing CpG Motifs
Other Activities of Oligodeoxynucleotides Containing CpG Motifs
Antisense Inhibition of Gene Expression by Steric Block
Antisense Inhibition of Gene Expression through Ribonuclease H-mediated Destruction of Target mRNA
Oligonucleotides in Vivo
Conclusions
Acknowledgements
References
Chemical Aspects
Chemistry of Oligonucleotides
Introduction
Design of Oligonucleotides
Oligonucleotide Modifications: Synthesis and Properties
Analysis of Oligonucleotides
Conclusion
Acknowledgement
References
The Oligonucleotide Prodrug Approach: The Pro-oligonucleotides
Introduction
What Kind of Enzymolabile Group?
First Pro-oligonucleotide Models
Pro-oligonucleotides of the Second Generation
Conclusion
Acknowledgements
References
Peptide Nucleic Acids
Introduction
Antisense
Antimicrobials
Anti-telomerase
Antigene
Anti-HIV
Pharmacology
Further Developments
Acknowledgement
References
Delivery
Peptide-mediated Delivery of Oligonucleotides
Delivery Vehicles for the Improved Uptake of Nucleic Acids: a Survey
The Potential of Peptides for Nucleic Acids Delivery
Strategies for the Coupling of Peptides to Oligonucleotides
Poly (L-lysine)-based Delivery Systems
Conjugation to Fusogenic Peptides Allowing Membrane Fusion or Membrane Translocation
Conclusions
Acknowledgements
References
Polymeric Nanoparticles and Microparticles as Carriers for Antisense Oligonucleotides
Introduction
Nanoparticles
In Vitro Stability of ONs Adsorbed onto Nanoparticles
Cell Interactions with ON Loaded Nanoparticles
In Vitro Pharmacological Activity of Oligonucleotide-loaded Nanoparticles
In Vivo Studies with Oligonucleotide Nanoparticles
Microparticles
Conclusion
References
Liposomes for the Delivery of Oligonucleotides
Introduction
Anionic Liposomes
Cationic Liposomes
pH-sensitive Liposomes
Immunoliposomes and Other Molecularly Targeted Liposomes
Fusogenic Liposomes and Proteoliposomes
Conclusions
References
Comb-type Polycation Copolymer for Antigene Strategy and DNA Carrier
Introduction
Comb-type Polycations as a Stabilizer for DNA Duplex and Triplex
Comb-type Polycation Copolymers with Cell-specific Polysaccharide Side-chains as cell-specific DNA Carrier
Acknowledgements
References
Biopharmaceutics
Delivery of Antisense Oligonucleotides in Vitro: Experimental Points
Introduction
Oligonucleotide-Binding Proteins on the Cell Surface
Intracellular Compartmentalization
Oligonucleotide Delivery Reagents - Practical Considerations
Experimental Antisense: Points to Consider
References
Mechanisms of Transmembrane Transport of Oligonucleotides
Overview of Cellular Uptake of Antisense Oligonucleotides
Permeation of Oligonucleotides across Membranes
Mechanisms of Enhancement of Oligonucleotide Permeation across Membranes
Summary
References
Pharmacokinetics of Oligodeoxynucleotides
Introduction
Pharmacokinetics
Chemistry of Oligonucleotides and Formulations
Cellular Pharmacokinetics
Preclinical Pharmacokinetics
Clinical Pharmacokinetics
Conclusions
References
Pharmacological Activity
Antisense as a Novel Therapy for Cancer
Novel Approaches for Anticancer Therapy
Antisense Approaches for Cancer
Antisense as a Novel Anticancer Approach against ras
Conclusions and Future Prospects
Acknowledgements
References
Modulation of Inflammatory Processes with Antisense Oligonucleotides
Introduction
ICAM-1, a Case Study
Other Examples
Regulation of Immune Response by Non-antisense Mechanisms
Conclusions
References
Oligonucleotides as Antiparasite Compounds
Introduction
Design of Antisense Oligonucleotides for Antiparasite Use
Antiparasite Effects of Antisense Oligonucleotides
RNA Structures are Valid Targets for Regulatory Oligonucleotides
Conclusion
Acknowledgements
References
Index