Non-Viral Vectors for Gene Therapy

Transcription

1 Non-Viral Vectors for Gene Therapy Second Editio n Part Leaf Huan g Mien-Chie Hun g Ernst Wagner

2

3 Contributors Preface xvi i xii i 1 BASIC CONCEPTS 1 Recent Advances in Non-viral Gene Delivery 3 Christine C. Conwell and Leaf Huan g I. Introduction 4 II. Cationic Lipids 4 III. Cationic Polymers 6 IV. Triggered Release 9 V. Physical Delivery Methods for Naked DNA 1 1 VI. Prospects 1 5 References Barriers to Gene Delivery Using Synthetic Vectors 1 9 Martin L. Read, Ann Logan, and Leonard W. Seymour I. Introduction 20 II. Extracellular Barriers 2 1 III. Intracellular Barriers 26 IV. Conclusions 40 References Pharmacokinetics of Plasmid DNA-Based Non-vira l Gene Medicine 4 7 Makiya Nishikawa, Yoshinobu Takakura, an d Mitsuru Hashida I. Introduction 4 8 II. How to Trace Plasmid DNA In Vivo 5 0 III. Pharmacokinetic Features of Naked Plasmid DNA After Intravascular Injection 5 2 IV. Pharmacokinetic Features of Plasmid DNA/Non-viral Vecto r Complex After Intravenous Injection 5 6 V. Pharmacokinetic Features After Tissue Injection 61

4 VI. Conclusion 6 2 References CATIONIC LIPOSOME S 4 What Role Can Chemistry Play in Cationic Liposome - Based Gene Therapy Research Today? 7 1 Kostas Kostarelos and Andrew D. Miller I. Introduction 7 2 II. AB Core Particles 7 4 III. ABD Particles 8 9 IV. ABC Particles 9 7 V. ABCD Particles 10 3 VI. The Future Role of Chemistry-B, C, and D Layer Innovations 10 6 VII. Main Abbreviations 10 8 References Lipoplex Structures and Their Distinct Cellular Pathways 119 Kai Ewert, Heather M. Evans, Ayesha Ahmad, Nelle L. Slack, Alison J. Lin, Ana Martin-Herranz, and Cyrus R. Safinya I. Introduction 12 0 II. Formation, Structures, and Stability of CL-DNA Complexes 12 2 III. Structure-Transfection Efficiency Relationships o f CL-DNA Complexes 12 8 IV. PEOylated CL-DNA Complexes: Surface Functionalization and Distinct DNA-DNA Interaction Regimes 142 V. Conclusion 147 VI. Future Directions 14 7 VIl. Main Abbreviations 149 References "Diffusible-PEG-Lipid Stabilized Plasmi d Lipid Particles" 15 7 Ian MacLachlan and Pieter Culli s I. Introduction 15 8 II. Properties of a Plasmid Delivery System for the Treatment o f Systemic Disease 158

5 III. Methods of Encapsulating Plasmid DNA 16 6 IV. Pharmacology of Encapsulated Plasmid DNA 17 3 V. Conclusion 18 2 References Toxicity of Cationic Lipid-DNA Complexes 189 Nelson S. Yew and Ronald K. Scheule I. Introduction 19 0 II. Acute Toxicity After Intrapulmonary Delivery 19 1 III. Biodistribution of Cationic Lipid-DNA Complexe s After Intravenous Delivery 194 IV. Acute Toxicity After Intravenous Delivery 195 V. Role of Immunostimulatory CpG Motifs in Cationic Lipid-DNA Toxicity 19 6 VI. Modifying the Plasmid DNA Vector to Decrease th e CpG Response 19 9 VII. Other Approaches to Reduce the Toxicity o f Cationic Lipid-DNA Complexes 205 VIII. Summary 20 9 References CATIONIC POLYMERS 8 Polyethylenimine (PEI) 21 7 Barbara Demeneix and Jean-Paul Behr I. Mechanism of Gene Delivery 21 8 II. Transfection of Cells in Culture 22 2 III. In Vivo Gene Delivery 22 4 References Pluronic Block Copolymers for Gene Delivery 23 1 Alexander Kabanov, Jian Zhu, and Valery Alakho v I. Introduction 23 2 II. Pluronic Block Copolymers: The Structur e and Nomenclature 234 III. Synthesis and Purification of Pluroni c Block Copolymers 23 6 IV. Micellization, Solubilization, and Formation of Gels 236 V. Biological Activities of Pluronic Block Copolymers 239

6 VI. Summary of Applications of Pluronic i n Gene Delivery 24 0 VII. Effects of Pluronic Block Copolymers in Vira l Gene Delivery 24 0 VIII. Pluronic Block Copolymers as Adjuvants for Non-Viral Vectors 24 2 IX. Pluronic-Polycation Graft/Block Copolymers for Gene Delivery 243 X. Effects of Pluronic Block Copolymers on Gen e Transfer Using Naked DNA 246 XI. Possible Mechanisms of Pluronic Effects o n Gene Delivery 24 8 XII. Conclusion 25 0 XIII. Main Abbreviations 250 References Terplex Gene Delivery System 263 Sung Wan Kim I. Polymeric Gene Delivery Systems 264 II. Design and Characterization of Terplex 26 6 III. In Vitro Vascular Cell Transfection 26 7 IV. Terplex/DNA for Myocardial Transfection 26 9 References Design of Polyphosphoester-DNA Nanoparticles fo r Non-Viral Gene Delivery 275 Hai-Quan Mao and Kam W. Leon g I. Introduction 27 6 II. Synthesis and Structures of PPE and PPA Gene Carriers 28 1 III. Polycationic PPAs-Structure-Property Relationship : DNA Compaction Capacity and Gen e Transfection Efficiency 28 7 IV. Polycationic PPEs-Effect of Sidechain Structure on Degradation of Carrier, DNA Release Rate, an d Transfection Efficiency 29 5 V. PPE with a Charge Center in the Backbone 299 VI. Summary 30 1 References 302

7 12 Development of HVJ Envelope Vector and Its Applicatio n to Gene Therapy 307 Yasufumi Kaneda, Seiji Yamamoto, and Toshihiro Nakajim a I. Introduction 30 8 II. Preparation of HVJ Envelope Vector 31 1 III. Gene Transfer to Cultured Cells Using HV J Envelope Vector 31 3 IV. Gene Transfer In Vivo Using HVJ Envelope Vector 31 5 V. Gene Therapy for Hearing Impairment Using HVJ Envelope Vector 31 8 VI. Approaches to Cancer Gene Therapy Using HVJ Envelope Vector 32 0 VII. Toward the Clinical Trial 326 VIII. Main Abbreviations 32 8 References Targeting of Polyplexes : Toward Synthetic Viru s Vector Systems 33 3 Ernst Wagner, Carsten Culmsee, and Sabine Boeckl e 1. Introduction 33 4 II. Extracellular Delivery: Tissue and Cell Targeting 33 4 III. Cellular Uptake and Intracellular Trafficking 33 9 IV. In Vivo Administration of Polyplexes and Applications 34 1 V. Optimizing Polyplexes Toward Synthetic Viruses 34 5 VI. Conclusions 34 7 VII. Main Abbreviations 34 7 References 34 8 Index 355