Taira / Kataoka / Niidome Non-viral Gene Therapy

Gene Design and Delivery
1. Auflage 2006
ISBN: 978-4-431-27879-5
Verlag: Springer Japan
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 487 Seiten

Autoren/Hrsg.

Taira, Kazunari

Kataoka, Kazunori

Niidome, Takuro

Inhaltsverzeichnis

1;Foreword;5
2;Preface;7
3;Contents;10
4;1. Molecules for Gene Therapy;13
4.1;Recent Progress in Non-viral Gene Delivery;14
4.1.1;1 Introduction;14
4.1.2;2 Delivery of Naked DNA by Physical Methods;14
4.1.3;3 Cationic Polymer-Based Non-viral Vectors;16
4.1.4;4 Lipid-Based Non-viral Vectors;17
4.1.5;5 Toxicity of Non-viral Vectors;18
4.1.6;References;18
4.2;Physical Chemistry of DNA-Carrier Complexes;22
4.2.1;1 Ordered and Disordered Structures in Compact DNA;22
4.2.2;References;28
4.3;Liposomes;30
4.3.1;1 Liposomal Drug Delivery Systems for Gene Delivery In Vivo;30
4.3.2;2 Targeting to a Less Accessible Site (Solid Tumor);36
4.3.3;3 Liposomal Gene Delivery Systems;39
4.3.4;References;42
4.4;Polymeric Gene Carriers;46
4.4.1;1 Introduction;46
4.4.2;2 Various Polymeric Carriers;47
4.4.3;3 Transfection Protocol Using Polyplexes;50
4.4.4;4 Biological Barriers;51
4.4.5;5 Conclusions;56
4.4.6;References;56
4.5;Development of a Supramolecular Nanocarrier for Gene Delivery Based on Cationic Block Copolymers;62
4.5.1;1 Introduction;62
4.5.2;2 Preparation of Block Copolymers as Gene Carriers;63
4.5.3;3 Polylysine-Based Non-viral Gene Delivery Systems;66
4.5.4;4 Environmentally Responsive Polycation-Based Non- viral Gene Carriers;67
4.5.5;5 Conclusions;70
4.5.6;References;70
4.6;Chitosan;74
4.6.1;1 Introduction;74
4.6.2;2 DNA/Chitosan Complexes;74
4.6.3;3 Chitosan Derivatives;78
4.6.4;4 Mechanism of Transcellular and Intracellular Transport of DNA/ Chitosan Complexes;80
4.6.5;5 DNA/Chitosan/Sugar-PEG-C Ternary Complexes;82
4.6.6;6 Conclusion;83
4.6.7;References;83
4.7;Dendrimers as DNA Carriers;86
4.7.1;1 Introduction;86
4.7.2;2 Transfection Ef.ciency;87
4.7.3;3 Factors Affecting Transfection Activity;89
4.7.4;4 Combining Dendrimers with Other Strategies;91
4.7.5;5 Dendrimer Conjugates;92
4.7.6;6 Conclusion;92
4.7.7;References;94
4.8;Use of Synthetic Peptides for Non-viral Gene Delivery;98
4.8.1;1 Introduction;98
4.8.2;2 Peptides as Cationic Moieties of Gene Carriers;98
4.8.3;3 Peptides as Ligands;104
4.8.4;4 Peptides as Tools for Endosome Disruption;106
4.8.5;5 Peptides as Signals for Transport to the Nucleus;108
4.8.6;6 Peptides as Sensors for Functional Gene Delivery;108
4.8.7;7 Prospects;110
4.8.8;References;110
4.9;An Oligonucleotide Carrier Based on b- 1,3- Glucans;114
4.9.1;1 Oligonucleotide/ b- 1,3- Glucan Complexes;114
4.9.2;2 Biofunctional Oligonucleotides, Antisense and CpG Oligonucleotides;115
4.9.3;3 Strategy and Chemistry;117
4.9.4;4 Delivery of CpG Motifs;119
4.9.5;5 Delivery of Antisense Oligonucleotides to Avoid Lysosomal Degradation;121
4.9.6;6 Conclusions;126
4.9.7;References;126
4.10;Biological and Chemical Hybrid Vectors;129
4.10.1;1 Introduction: Concept of the Hybrid Vector;129
4.10.2;2 Fusogenic Liposome: A Delivery Vehicle Mimicking Envelope Viruses;131
4.10.3;3 Peptide-Displaying Phage Particles: Delivery Vehicles Mimicking Non- envelope Viruses;134
4.10.4;4 Construction of Stable Replicons;137
4.10.5;5 Future Perspectives: Towards the Development of Ideal Hybrid Vectors;139
4.10.6;References;140
5;2. Controlled Gene Delivery;144
5.1;Pharmacokinetics of Gene Delivery in Cells;145
5.1.1;1 Introduction;145
5.1.2;2 A New Packaging Concept for Non-viral Vectors for Ef . cient Gene Delivery: Programmed Packaging;147
5.1.3;3 Control of the Intracellular Traf.cking of Genes;148
5.1.4;4 Optimization of Intracellular Traf.cking: Pharmacokinetic Considerations;156
5.1.5;5 Conclusions;159
5.1.6;References;160
5.2;Active DNA Release from Complexes;165
5.2.1;1 Introduction;165
5.2.2;2 pH-Responsive Vectors;167
5.2.3;3 Redox-Responsive Vectors;168
5.2.4;4 Photo-Responsive Vectors;170
5.2.5;5 Conclusions;171
5.2.6;References;172
5.3;Controlled Release of DNA Using Thermoresponsive Polymers;175
5.3.1;1 Signi.cance of DNA Release from Synthetic Gene Carriers;175
5.3.2;2 Stimuli-Responsive Synthetic DNA Carriers;176
5.3.3;3 Temperature-Responsive Polymers and Their Applications;178
5.3.4;4 DNA Carrier Systems Using Temperature-Responsive Polymers: Temperature- Responsive Polymeric Vector Systems;179
5.3.5;References;184
5.4;Active Transport of Exogenous Genes into the Nucleus;186
5.4.1;1 Introduction;186
5.4.2;2 Nuclear-Pore Complex and Nuclear Import of Karyophilic Proteins;187
5.4.3;3 Nuclear Import of Virus Genomes;189
5.4.4;4 Nuclear Import of DNA Conjugated with NLS Peptides;189
5.4.5;5 Nuclear Import of DNA Conjugated with DNA- Binding Proteins;191
5.4.6;6 Nuclear Import of DNA Conjugated with Viral Proteins;192
5.4.7;7 Nuclear Import of DNA Directly Conjugated with Importins;192
5.4.8;8 Nuclear Import of DNA with a Glycosylated Carrier;192
5.4.9;9 Conclusions;193
5.4.10;References;193
5.5;Controlled Intracellular Localization of Oligonucleotides by Chemical Conjugation;197
5.5.1;1 Introduction;197
5.5.2;2 Synthesis of Oligonucleotide-Peptide Conjugates by Solid- Phase Fragment Condensation;197
5.5.3;3 Nuclear and Cytoplasmic Localization of Oligonucleotide- Peptide Conjugates;199
5.5.4;4 Mechanisms of Cellular Uptake of Oligonucleotide- Peptide Conjugates;204
5.5.5;References;205
5.6;Functional Nucleotide Sequences Capable of Promoting Non- viral Genetic Transfer;208
5.6.1;1 Introduction;208
5.6.2;2 Plasmid Vectors as an Important Component of Non- viral Gene Delivery Systems;208
5.6.3;3 Plasmid Vector Sequence Crucially Affects the Ef.cacy of Non- viral Gene Transfer;209
5.6.4;4 Epstein-Barr Virus-Based Plasmid Vectors;213
5.6.5;5 The Sleeping Beauty Transposable Element;214
5.6.6;6 Conclusions;216
5.6.7;References;216
5.7;Shielding of Cationic Charge of the DNA Complex to Avoid Nonspeci . c Interactions for In Vivo Gene Delivery;221
5.7.1;1 Introduction;221
5.7.2;2 Interaction of DNA Complexes with Blood Components or Extracellular Matrices;222
5.7.3;3 Size Control of DNA Complexes;228
5.7.4;4 Transcription-Activating Effect of Polyanions and Polyampholytes: Ionized PEGs as Arti . cial HMG Proteins;231
5.7.5;References;233
5.8;In Vivo Gene Transfer by Ligand- Modi . ed Gene Carriers;236
5.8.1;1 Introduction;236
5.8.2;2 Biodistribution Characteristics of Naked pDNA;237
5.8.3;3 Biodistribution Characteristics of pDNA Complexed with Cationic Liposomes;238
5.8.4;4 Biological Barriers to Gene Delivery;238
5.8.5;5 In Vivo Receptor-Mediated Gene Delivery;240
5.8.6;References;244
5.9;Optimizing Polyplexes into Synthetic Viruses for Tumor- Targeted Gene Therapy;247
5.9.1;1 Introduction;247
5.9.2;2 Shielded Ligand-PEI Polyplexes for Tumor-Targeted Gene Transfer;248
5.9.3;3 Development of Novel Polymers as DNA Carriers;249
5.9.4;Shielding from non- specific interaction;250
5.9.5;4 Bioresponsive Elements for Optimizing Polyplexes into Synthetic Viruses;252
5.9.6;5 Conclusions;253
5.9.7;References;253
5.10;Gene Transfer and Target Diseases;256
5.10.1;1 Gene Transfer and Target Diseases;256
5.10.2;2 Cardiovascular Diseases;256
5.10.3;3 Cancer;261
5.10.4;4 Conclusions;262
5.10.5;References;263
5.11;Clinical Trials Using Non-viral Gene Delivery Systems;271
5.11.1;1 Introduction;271
5.11.2;2 Clinical Trials Using Cationic Lipid Gene Transfer;272
5.11.3;References;298
6;3. Current Protocols of Gene Delivery;301
6.1;Evaluation of Size and Zeta Potential of DNA/ Carrier Complexes;302
6.1.1;1 Introduction;302
6.1.2;2 Materials;303
6.1.3;3 Methods;303
6.1.4;4 Results;305
6.1.5;References;308
6.2;Observation of DNA/Carrier Complexes Under Fluorescence Microscopy;309
6.2.1;1 Introduction;309
6.2.2;2 Principle of Single Molecular Observation by Fluorescence Microscopy;310
6.2.3;3 Fluorescent Dyes for Observing DNA Molecules;311
6.2.4;4 Fluorescence Microscopy and the Recording System;311
6.2.5;5 Sample Preparation;312
6.2.6;6 Measurement of DNA Size in Solution;312
6.2.7;7 Observation of Each Component of the DNA Polyion Complex;313
6.2.8;8 Observation of the DNA Interaction with Cells;313
6.2.9;9 Attachment of the DNA Complexes onto Charged or Protein- Immobilized Beads;314
6.2.10;References;315
6.3;Synthesis of Chemically Modi.ed Chitosan and a Study of Its Gene Transfection Ef . ciency;316
6.3.1;1 Introduction;316
6.3.2;2 Materials;318
6.3.3;3 Methods;318
6.3.4;References;323
6.4;Newly Designed DNA Fragments for Gene Correction;324
6.4.1;1 Introduction;324
6.4.2;2 Materials;325
6.4.3;3 Methods;326
6.4.4;References;330
6.5;Evaluation of Gene Expression In Vivo After Intravenous and Intraportal Administration of Lipoplexes;332
6.5.1;1 Introduction;332
6.5.2;2 Materials;333
6.5.3;3 Methods;334
6.5.4;References;338
6.6;Evaluation by Southern Blot Hybridization of DNA Administered with a Gene Carrier to Organs;340
6.6.1;1 Introduction;340
6.6.2;2 Materials;341
6.6.3;3 Methods;341
6.6.4;4 Biodistribution and Pharmacokinetics of Intravenously Injected DNA with Gene Carriers;346
6.6.5;References;347
6.7;Evaluation of the Immune Response After Administration of Plasmid DNA- Non- viral Vector Complexes;348
6.7.1;1 Introduction;348
6.7.2;2 Materials and Methods;349
6.7.3;3 Comments;353
6.7.4;References;354
6.8;Gateway RNAi;357
6.8.1;1 Introduction;357
6.8.2;2 Gateway;358
6.8.3;3 Experimental Protocols;360
6.8.4;4 Application of Gateway System;360
6.8.5;5 Conclusions;365
6.8.6;References;368
7;4. Design of Genes Based on Current RNA Technology;370
7.1;Design of Intracellularly Active Ribozymes and siRNAs;371
7.1.1;1 Ribozymes;371
7.1.2;2 siRNAs, siRNA-Expression Vectors, and siRNA- Expression Library;388
7.1.3;3 Concluding Remarks;397
7.1.4;References;398
7.2;RNAi-Based Inhibition Speci.c for Mutant Alleles in Autosomal Dominant Diseases: Sequence- Dependent and - Independent Discrimination of Mutant and Wild- Type Alleles by siRNA;406
7.2.1;1 Introduction;406
7.2.2;2 Optimal Location of a Mutation for Discriminating Among Point Mutations in Familial ALS;406
7.2.3;3 siRNA Speci.c for G93A SOD1 with Point Mutation in Familial ALS;407
7.2.4;4 siRNA Speci.c for the Mutant Allele in Machado- Joseph Disease Using a Polymorphorism Related to CAG Repeat Length;408
7.2.5;5 Sequence-Independent Discriminations of Mutant and Wild- Type Alleles by siRNA;410
7.2.6;6 Discussion;410
7.2.7;References;412
7.3;In Vivo RNA Interference: Another Tool in the Box?;413
7.3.1;1 Introduction;413
7.3.2;2 First In Vivo RNAi Proof-of-Concept Experiment: Inoculation of siRNA;414
7.3.3;3 Transgenic: Random Integration of shRNA- Expressing Constructs;416
7.3.4;4 Transgenic Models: Targeted Insertion Approach;419
7.3.5;5 Future Development of In Vivo RNAi;420
7.3.6;6 Conclusion;426
7.3.7;References;427
7.4;Suppression of Gene Expression via Chromatin Remodeling and the siRNAInduced Silencing of Transcription;431
7.4.1;1 Epigenetics;431
7.4.2;2 Post-transcriptional Gene Silencing;432
7.4.3;3 Transcriptional Gene Silencing;433
7.4.4;4 RNAi-Induced Methylation of DNA in Human Cells;436
7.4.5;5 Chromatin-Remodeling Complexes and RNAi;436
7.4.6;6 Conservation of siRNA-Induced TGS and Methylation in Various Species;439
7.4.7;7 siRNA-Directed Methylation of the Genome;440
7.4.8;8 Concluding Remarks;443
7.4.9;References;443
7.5;Intracellular Delivery of Nucleic Acids: Differences Between Transfection and siFection Re . ect Differences Between DNA and RNA, and Between Oligodeoxynucleotides and Oligonucleotides;449
7.5.1;1 Introduction;449
7.5.2;2 Delivery of Short, Double-Stranded Synthetic RNA — siFection;452
7.5.3;3 Discussion;454
7.5.4;4 Summary;457
7.5.5;References;458
7.6;In Vivo Antitumor Activity of a New Cationic Liposome siRNA Complex;464
7.6.1;1 Introduction;464
7.6.2;2 A New Cationic Liposome, LIC-101;465
7.6.3;3 Composition and Formulation of LIC-101;465
7.6.4;4 Intracellular Delivery of Liposome/Nucleic Acid Complexes;466
7.6.5;5 Biological Activity of siRNA;467
7.6.6;6 Discussion;471
7.6.7;7 Concluding Remarks;471
7.6.8;References;472
7.7;Enhancing RNAi with Synthetic RNA Duplexes;473
7.7.1;1 Introduction to siRNA-Mediated Silencing;473
7.7.2;2 Characterization of siRNAs Produced from 27-mers;476
7.7.3;3 Testing 27-mers Against Endogenous Targets;479
7.7.4;4 Testing for Interferon Pathway Activation and Off- Target Effects of 27- mers;480
7.7.5;5 Delivery of Synthetic RNAs;482
7.7.6;References;482
8;Subject Index;484