| |
| |
| 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 | |