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14 Adenovirus-mediated siRNA Delivery to Cancer 309
- Authors
- Yun, C.-O.
- Issue Date
- Jun-2013
- Publisher
- John Wiley and Sons
- Abstract
- Vector-based approaches have the potential to provide stable introduction of RNAi. In principle, it requires only a single treatment with shRNA vector to target a specific gene. This chapter describes novel strategies to develop more powerful shRNA expression vectors for the treatment of cancer, with a focus on adenoviral systems.
- Table Of Contents
- 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 2.3 Methods for Analysis of siRNA 26 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 3.3 Safety Issues of RNAi Mediators 50 3.4 Efficacy of RNAi Mediators 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 4.4 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 5.3 miRNA-based shRNAs 96 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 6.3 Bioconjugates for Site-specific Delivery 120 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 7.3 Polymeric Multifunctional siRNA Delivery Systems 150 7.4 Conclusion 157 References 157 8 Dendrimers in RNAi Delivery 163 Jose Luis Jimenez Fuentes, Paula Ortega, Sara Ferrando-Martýnez, 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 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 9.3 Safety Assessment of Nanocarrier and Design of Safe MSNP Carrier 199 References 179 9.4 Summary References 202 10 Environmentally-Responsive Nanogels for siRNA Delivery 207 Atsushi Tamura and Yukio Nagasaki 10.1 Introduction 207 10.2 Reductive Environment-Responsive Disulfide Crosslinked Nanogels 209 10.3 Temperature-Responsive Nanogels 211 10.4 pH-Responsive Nanogels 212 10.5 PEGylated and Partially Quaternized Polyamine Nanogels 216 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 11.6 Tissue-specific Transduction 233 11.7 Applications of Virally Expressed shRNAs 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 13.5 Advanced Delivery 283 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 14.2 shRNA-expressing Adenoviruses: Cancer Biological Studies and Therapeutic Implications 312 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 15.3 RNAi in Hepatocellular Carcinoma 336 15.4 RNAi in Liver Fibrosis 340 15.5 Delivery Systems in RNAi 345 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 16.2 Vectors Suitable for Hepatic Delivery of HBV Gene Silencers 369 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 17.3 Delivery and Development of RNAi Therapies for Respiratory Disease 397 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 18.5 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 19.3 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 20.3 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 20.6 Utility of MicroRNA Sponge in Living Organisms 496 20.7 Future Perspectives 498 References 499 Index 505
- Pages
- 536
- Start Page
- 309
- End Page
- 326
- ISBN
- 978-1-119-97686-8
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