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Produktbild: Advanced Delivery and Therapeutic Applications of RNAi

Advanced Delivery and Therapeutic Applications of RNAi

219,99 €

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Beschreibung

Produktdetails

Einband

Gebundene Ausgabe

Erscheinungsdatum

04.06.2013

Herausgeber

Kun Cheng + weitere

Verlag

John Wiley & Sons Inc

Seitenzahl

534

Maße (L/B/H)

25,2/17,5/3 cm

Gewicht

980 g

Auflage

1. Auflage

Sprache

Englisch

ISBN

978-1-119-97686-8

Beschreibung

Produktdetails

Einband

Gebundene Ausgabe

Erscheinungsdatum

04.06.2013

Herausgeber

Verlag

John Wiley & Sons Inc

Seitenzahl

534

Maße (L/B/H)

25,2/17,5/3 cm

Gewicht

980 g

Auflage

1. Auflage

Sprache

Englisch

ISBN

978-1-119-97686-8

Herstelleradresse

Libri GmbH
Europaallee 1
36244 Bad Hersfeld
DE

Email: GPSR Kontakt

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  • Produktbild: Advanced Delivery and Therapeutic Applications of RNAi
  • Preface xvii

    Contributors xix

    About the Editors xxiii

    Part 1 Introduction and Basics of RNAi 1

    1 Mechanisms and Barriers to RNAi Delivery 3
    Jiehua Zhou and John J. Rossi

    1.1 Introduction 3

    1.2 Barriers to Systemic RNAi Delivery 5

    1.3 Rational Design to Improve RNAi Efficacy 6

    1.4 Chemical Modifications to Enhance siRNA Stability and Reduce Immune Response 7

    1.5 Cellular Uptake and Intracellular Release of siRNA 7

    1.6 Combinatorial Targeting for Targeted RNAi Delivery 8

    1.7 Cell-Specific Aptamer-Functionalized Nanocarriers for RNAi Delivery 9

    1.8 The Clinical Development and Challenges of siRNAs Therapeutics 10

    1.9 Conclusion and Perspectives 12

    References 12

    2 Analysis of siRNA Delivery Using Various Methodologies 19
    Yi Pei

    2.1 Introduction 19

    2.2 Checkpoints for Analyzing siRNA Delivery 20

    2.2.1 Circulation Checkpoint 22

    2.2.2 Organ or Tissue Checkpoint 22

    2.2.3 Cellular Checkpoint 22

    2.2.4 RISC Checkpoint 23

    2.2.5 Target mRNA Knockdown (Indirect Checkpoint) 24

    2.2.6 Protein and Outcome (Indirect Checkpoint) 25

    2.2.7 Safety (Indirect Checkpoint) 26

    2.3 Methods for Analysis of siRNA 26

    2.3.1 General Considerations 26

    2.3.2 Hybridization-Based (Non-Imaging) Methods 28

    2.3.3 Non-Hybridization-Based (Non-Imaging) Methods 34

    2.3.4 Imaging-Based (Non-Hybridization) Methods 35

    2.3.5 Imaging-Based (Hybridization) Methods 37

    2.4 Case Study for siRNA Delivery Analysis 38

    References 39

    3 Challenges and Opportunities in Bringing RNAi Technologies from Bench to Bed 45
    Sandesh Subramanya and Lance Ford

    3.1 Introduction 45

    3.2 RNAi Mediator (siRNA or shRNA) 45

    3.2.1 siRNA 45

    3.2.2 Vector-derived shRNA 47

    3.2.3 miRNAs 49

    3.3 Safety Issues of RNAi Mediators 50

    3.3.1 Immune Stimulation 50

    3.3.2 RNAi Over expression 52

    3.4 Efficacy of RNAi Mediators 52

    3.4.1 Therapeutic Response 52

    3.5 RNAi Mediators in Clinical Trials 53

    3.6 Conclusion 54

    References 55

    Nonclinical Safety Assessments and Clinical Pharmacokinetics for Oligonucleotide Therapeutics: A Regulatory Perspective 63
    Shwu-Luan Lee, Paul Brown, Jian Wang and Robert T. Dorsam

    4.1 Introduction 63

    4.2 Unique Properties of Oligonucleotide-based Therapeutics 63

    4.3 Regulation of Oligonucleotide-Based Therapeutics 65

    4.3.1 Submission to the FDA 65

    4.3.2 Review Process for Non-clinical Studies 67

    4.3.3 Regulatory Issues 74

    4.3.4 Clinical Pharmacokinetics 76

    4.4 Conclusion 79

    Disclaimer 79

    Appendix 79

    References 80

    Role of Promoters and MicroRNA Backbone for Efficient Gene Silencing 83
    Feng Li and Ram I. Mahato

    5.1 Introduction 83

    5.2 Promoters for shRNA Expression 84

    5.2.1 Constitutive Promoters 84

    5.2.2 Inducible Promoters 87

    5.2.3 Site Specific Promoters 93

    5.3 miRNA-based shRNAs 96

    5.3.1 miRNA-based shRNA Enhances Gene Silencing 96

    5.3.2 miRNA-based shRNA Reduces Toxicities 97

    5.3.3 Application of miRNA-based shRNA for Combination Gene Therapy 98

    5.4 Concluding Remarks 100 References 101

    Part 2 RNAi Delivery Strategies 109

    6 Bioconjugation of siRNA for Site-specific Delivery 111
    Bin Qin, Wei Jin and Kun Cheng

    6.1 Introduction 111

    6.2 Conjugation Strategy 112

    6.2.1 RNA Chemical Modification 112

    6.2.2 Site of Conjugation 114

    6.2.3 Conjugation Chemistry 115

    6.3 Bioconjugates for Site-specific Delivery 120

    6.3.1 Antibody-siRNA Bioconjugates 120

    6.3.2 Aptamer-siRNA Bioconjugates 122

    6.3.3 Peptide-siRNA Bioconjugates 124

    6.3.4 Lipid-siRNA Bioconjugates 126

    6.3.5 Others 128

    6.4 Conclusion 129

    References 129

    7 Multifunctional RNAi Delivery Systems 137
    China Malakondaiah Kummitha, Anthony S. Malamas and Zheng-Rong Lu

    7.1 Introduction 137 7.1.1 Chapter Objectives 139

    7.2 Lipid-Based Delivery Systems 139

    7.2.1 Cationic Lipids 139

    7.2.2 Ionizable Cationic Lipids 140

    7.2.3 Lipid-Like Materials 140

    7.2.4 pH-sensitive Surfactants as Multifunctional siRNA Carriers 142

    7.3 Polymeric Multifunctional siRNA Delivery Systems 150

    7.3.1 Polyethylenimine 150

    7.3.2 Chitosan 151

    7.3.3 Cyclodextrins 152

    7.3.4 Dendrimers 152

    7.3.5 Polyalkylacrylic Acid-based pH-sensitive Polymers 153

    7.3.6 Other pH-sensitive Polymers 156

    7.4 Conclusion 157

    References 157

    8 Dendrimers in RNAi Delivery 163
    Jose Luis Jimenez Fuentes, Paula Ortega, Sara Ferrando-Mart?nez, Rafael Gomez, Manuel Leal, Javier de la Mata and MaAngeles Munoz-Fernandez

    8.1 Introduction 163

    8.2 Challenges in RNAi Delivery 164

    8.3 Dendrimers as Non Viral Vectors 166

    8.3.1 Dendritic Architectures 166

    8.3.2 Synthesis of Dendrimers 168

    8.3.3 Types of Dendrimers in Drug Delivery 169

    9 Development of Pharmaceutically Adapted Mesoporous Silica Nanoparticles for siRNA Delivery 187
    Wilson X. Mai, Tian Xia and Huan Meng

    9.1 Introduction 187

    9.2 Mesoporous Silica Nanoparticles as Novel Inorganic Nanocarriers for siRNA Delivery 188

    9.2.1 Discovery and Synthesis 188

    9.2.2 Surface Modification of MSNP for Nucleic Acid Delivery 190

    9.2.3 MSNP for Dual siRNA and Drug Delivery 191

    9.2.4 Improving in vivo Implementation of MSNP-Based Delivery Platform 196

    9.2.5 Design of Pharmaceutically Adapted MSNP via the Knowledge Generated by Discoveries at the Nano/Bio Interface 197

    9.3 Safety Assessment of Nanocarrier and Design of Safe MSNP Carrier 199

    9.3.1 Safety of Nanocarriers 199

    9.3.2 Safe Design of MSNP Carrier 201

    References 179

    9.4 Summary References 202

    10 Environmentally-Responsive Nanogels for siRNA Delivery 207
    Atsushi Tamura and Yukio Nagasaki

    10.1 Introduction 207

    10.1.1 siRNA Delivery System 207

    10.1.2 Crosslinked Nanogels for siRNA Delivery 208

    10.2 Reductive Environment-Responsive Disulfide Crosslinked Nanogels 209

    10.3 Temperature-Responsive Nanogels 211

    10.4 pH-Responsive Nanogels 212

    10.4.1 Acid-degradable Nanogels for Intracellular Release of siRNA 212

    10.4.2 Design of pH-Responsive PEGylated Nanogels with Endosomal Escape Ability 212

    10.4.3 Cytoplasmic Delivery of PEGylated Nanogel/siRNA Complexes 214

    10.5 PEGylated and Partially Quaternized Polyamine Nanogels 216

    10.5.1 Design of Quaternized Polyamine Nanogels 216

    10.5.2 Enhanced Cellular Uptake of siRNA by Quaternized Polyamine Nanogels 216

    10.5.3 Enhanced Gene-Silencing Activity of Quaternized Polyamine Nanogel/siRNA Complexes 219

    10.6 Conclusions 220

    References 220

    11 Viral-Mediated Delivery of shRNA and miRNA 225
    Fredric P. Manfredsson

    11.1 Introduction 225

    11.2 RNAi - A Brief Overview 226

    11.3 shRNA or miRNA? 226

    11.4 Rational Design 227

    11.5 Viral Vectors 227

    11.5.1 Recombinant Adeno-associated Virus (rAAV) 229

    11.5.2 Retrovirus (RV) 230

    11.5.3 Lentivirus (LV) 230

    11.5.4 Adenovirus (AD) 231

    11.5.5 Herpes Simplex Virus (HSV) 231

    11.5.6 Baculovirus (BV) 232

    11.5.7 Poxvirus 232

    11.6 Tissue-specific Transduction 233

    11.6.1 CNS 233

    11.6.2 Ocular 234

    11.6.3 Respiratory System 235

    11.6.4 Liver 236

    11.6.5 Skeletal Muscle 237

    11.6.6 Heart 237

    11.6.7 Systemic 238

    11.6.8 Ex Vivo 238

    11.6.9 Cell Culture 238

    11.6.10 Transcription Cassettes 239

    11.7 Applications of Virally Expressed shRNAs 241

    11.7.1 Virally Mediated "Knockouts" 241

    11.7.2 Concomitant Expression of Therapeutic Genes 241

    11.8 Viral Gene Therapy in the Clinic 241

    11.9 Conclusion 242

    References 242

    12 The Control of RNA Interference with Light 255
    Simon H. Friedman

    12.1 Introduction 255 12.2 The Importance of Gene Expression 255

    12.3 Light Control of Gene Expression 257

    12.4 Why Use RNA Interference as a Basis for Light Control of Gene Expression? 258

    12.5 Light Activated RNA Interference (LARI), the work of Friedman and Co-Workers 259

    12.6 Work of McMaster and Co-Workers, 50 Antisense Phosphate Block 262

    12.7 Work of Heckel and Co-Workers, Nucleobase Block 263

    12.8 Use of 20 FsiRNA, work of Monroe and Co-Workers 264

    12.9 Photochemical Internalization 265

    12.10 Future Directions and Conclusions 266

    Acknowledgments 267

    References 267

    Part 3 Applications of RNAi in Various Diseases 269

    13 RNAi in Cancer Therapy 271
    Cristian Rodriguez-Aguayo, Arturo Chavez-Reyes, Gabriel Lopez-Berestein and Anil K. Sood

    13.1 Introduction 271

    13.2 Therapeutic Opportunities for Noncoding RNAs 274

    13.3 RNAs as Drugs 277

    13.4 Overcoming Anatomical and Physiologic Barriers 278

    13.4.1 Intravascular Degradation 279

    13.4.2 Tissue and Intracellular Delivery 280

    13.4.3 Immune-mediated Toxic Effects 281

    13.4.4 Nanocarrier-mediated Toxic Effects 282

    13.5 Advanced Delivery 283

    13.5.1 Localized siRNA Delivery 285

    13.5.2 Systemic siRNA Delivery 288

    13.5.3 Targeted siRNA Delivery 291

    13.5.4 Monitoring Delivery and Therapeutic Response 293

    13.6 Clinical Experience 294

    13.7 The Next Steps 298

    Acknowledgments 298

    References 298

    14 Adenovirus-mediated siRNA Delivery to Cancer 309
    Chae-Ok Yun

    14.1 Introduction 309

    14.1.1 shRNA-expressing Vectors 310

    14.1.2 Adenovirus Vectors 311

    14.2 shRNA-expressing Adenoviruses: Cancer Biological Studies and Therapeutic Implications 312

    14.2.1 Oncogene-targeted shRNA-expressing Ads 312

    14.2.2 shRNA-expressing Adenoviruses that Target Anti-apoptotic Genes 314

    14.3 Exploiting Oncolytic Adenovirus for siRNA Expression 315

    14.4 Current Limitations of Adenovirus-mediated siRNA Therapy and Future Directions: Smart Adenovirus Nanocomplexes Expressing siRNA for Systemic Administration 318

    14.5 Conclusion 320

    References 321

    15 RNAi in Liver Diseases 327
    Jiang Li, Jianqin Lu, Yifei Zhang, Mohammed Ghazwani, Peng Zhang, Xiang Gao and Song Li

    15.1 Introduction 327

    15.2 RNAi in Viral Hepatitis 327

    15.2.1 Hepatitis B 328

    15.2.2 RNAi of HBV Infection via siRNA/shRNA 329

    15.2.3 RNAi of HBV Infection via miRNAs 330

    15.2.4 Hepatitis C 332

    15.2.5 RNAi of HCV Infection via siRNA/shRNA 333

    15.2.6 RNAi of HCV Infection via miRNAs 335

    15.3 RNAi in Hepatocellular Carcinoma 336

    15.3.1 RNAi of HCC via siRNA/shRNA 337

    15.3.2 RNAi of HCC via miRNAs 338

    15.4 RNAi in Liver Fibrosis 340

    15.4.1 RNAi of Liver Fibrosis via siRNA/shRNA 341

    15.4.2 RNAi of Liver Fibrosis via miRNAs 343

    15.5 Delivery Systems in RNAi 345

    15.5.1 Liver Anatomy 346

    15.5.2 Viral Delivery Systems 346

    15.5.3 Non-Viral Delivery Systems 347

    15.5.4 Cell-specific Targeting Strategies 348

    15.5.5 Cellular Events after the Uptake of Nucleic Acid-Carrier Complexes 349

    15.5.6 Lipid-based Delivery Systems 350

    15.5.7 Polymer-Based Systems 350

    15.5.8 Calcium Phosphate-Lipid Hybrid System 351

    15.5.9 Hydrophobitized Nucleic Acid Derivatives 351

    15.5.10 Targeted Delivery to Tumor Blood Vessels 351

    15.6 Conclusion 352

    Acknowledgments 353

    References 353

    16 Approaches to Delivering RNAi Therapeutics that Target Hepatitis B Virus 367
    Carol Crowther, Mohube Betty Mowa, Abdullah Ely and Patrick Arbuthnot

    16.1 Introduction 367

    16.1.1 RNAi Therapeutics 368

    16.1.2 Hepatitis B Virus as a Target for RNAi-based Gene Silencing 369

    16.2 Vectors Suitable for Hepatic Delivery of HBV Gene Silencers 369

    16.2.1 Viral Vectors 370

    16.2.2 Nonviral Vectors 377

    16.3 Conclusions 381

    Acknowledgments 382

    References 382

    17 RNAi in Respiratory Diseases 391
    Ciara Kelly, Awadh B. Yadav, Paul J. McKiernan, Catherine M. Greene and Sally-Ann Cryan

    17.1 Introduction 391

    17.2 Respiratory Disease and RNA Interference 392

    17.2.1 RNAi in Lung Cancer 393

    17.2.2 RNAi to Treat Respiratory Infections 393

    17.2.3 RNAi in Inflammatory Lung Disease 394

    17.3 Delivery and Development of RNAi Therapies for Respiratory Disease 397

    17.3.1 Inhalation of RNA-medicines 397

    17.3.2 Chemical Modifications of siRNA 399

    17.3.3 RNAi Vectors 400

    17.3.4 RNAi Therapy In Vivo 405

    17.4 Conclusions 408

    Acknowledgements 408 References 408

    18 RNAi in Ocular Diseases 417
    Andrey Turchinovich, Georg Zoidl and Rolf Dermietzel

    18.1 Introduction 417

    18.2 The Principle of RNAi 418

    18.3 In vivo Delivery of siRNA 419

    18.4 Delivery of siRNA into the Eye 420

    18.4.1 Routes for Ocular Delivery of siRNA 420

    18.4.2 Delivery of Naked siRNA 421

    18.4.3 Delivery of siRNA Using Carriers 425

    18.4.4 Viral Delivery of shRNA 429

    18.5 Conclusions 431

    Abbreviations 432

    References 432

    19 micro RNAs as Therapeutic Agents and Targets 439
    D.S. Karolina and K. Jeyaseelan

    19.1 Introduction 439

    19.2 miRNA Therapeutics 440

    19.2.1 Therapeutic miRNA Inhibition 443

    19.2.2 Therapeutic miRNA Mimicry 446

    19.3 MicroRNAs and Cancer 447

    19.4 MicroRNAs in Stroke 450

    19.5 MicroRNAs in Heart Diseases 452

    19.6 MicroRNAs in Diabetes Mellitus 454

    19.7 MicroRNAs in Liver Diseases 457

    19.8 MicroRNAs and Ocular Diseases 461

    19.9 MicroRNAs and Respiratory Diseases 462

    19.10 MicroRNAs and Stem Cell Research 465

    19.11 Conclusion 468

    References 469

    20 Delivery of Micro RNA Sponges for Interrogation of MicroRNA Function In Vitro and In Vivo 483
    Jiakai Lin and Shu Wang

    20.1 MicroRNA Loss-of-Function Studies 483

    20.2 Considerations in MicroRNA Sponge Design 486

    20.2.1 Vector 486

    20.2.2 Promoter 487

    20.2.3 Reporter Gene 488

    20.2.4 MicroRNA Binding Sites 488

    20.3 Advantages and Limitations of MicroRNA Sponge over Other MicroRNA Loss-of-Function Strategies 489

    20.4 Interrogating MicroRNA Function via Transient MicroRNA Sponge Expression 493

    20.5 Interrogating MicroRNA Function via Stable MicroRNA Sponge Expression 494

    20.5.1 MicroRNA and Cell Differentiation 494

    20.5.2 MicroRNAs in Disease Development 495

    20.6 Utility of MicroRNA Sponge in Living Organisms 496

    20.6.1 MicroRNA Knockdown in Plants 496

    20.6.2 MicroRNA Knockdown in Mouse 497

    20.6.3 MicroRNA Knockdown in Drosophila Melanogaster 498

    20.7 Future Perspectives 498

    References 499

    Index 505