Integration of Biomaterials for Gene Therapy

Rishabha Malviya, PhD, is an associate professor in the Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University. He has authored more than 150 research/review papers for national/international journals. He has been granted more than 10 patents from different countries while a further 40 patents are published/under evaluation. He has edited multiple volumes for Wiley-Scrivener.

Sonali Sundram completed her M. Pharm from Dr. A. P. J. Abdul Kalam Technical University, Lucknow, India and she is now a research scientist at King George’s Medical University, Lucknow as well as an assistant professor at Galgotias University, Greater Noida. She has more than 8 patents to her credit and edited 6 books with international publishers.

Foreword xvii

Preface xix

Acknowledgment xxi

1 Biocompatible Hydrogels for Gene Therapy: Advancement and Applications 1
Ankita Gupta and Swatantra K.S. Kushwaha

1.1 Introduction 2

1.2 Hydrogels Classification 3

1.3 Fabrication of Hydrogels and Its Desirable Technical Features 4

1.4 Factors to be Tuned for Gene Encapsulation in Hydrogels 4

1.5 Recent Advances on Hydrogels for Gene Delivery 6

1.6 Conclusion 9

2 Use of Polysaccharides: Novel Delivery System for Genetic Material 13
Prashant Kumar, Swatantra K.S. Kushwaha, Neelottama Kushwaha, Abhishek Singh and Surya Nath Pandey

2.1 Introduction 14

2.2 Cross-Linking Techniques for Engineering Polysaccharides-Based Biomaterials 23

2.3 Approaches to Design Polysaccharide-Derived Biomaterials 26

2.4 Biomedical Applications of Polysaccharide-Derived Biomaterials 29

2.5 Advanced Biomaterials for Wound Dressings 30

2.6 Scaffolds for Tissue Engineering and Development of Bioinks for 3D Bioprinting 30

2.7 Recent Utilization of Polysaccharides 31

2.8 Toxicity Concerns of Polysaccharide-Derived Biomaterials 33

2.9 Preclinical and Clinical Studies on Gene Delivery Using Polysaccharide-Based Biomaterials 33

2.10 Challenges and Future Directions 34

2.11 Future Prospects 35

2.12 Conclusion 35

3 Polysaccharide-Based Biomaterials for Gene Delivery 47
Ankita Moharana, Abhitav Tiwari, Shalini Perada, Shivlal Yadav and Om Prakash Kumar

3.1 Background 48

3.2 Introduction 49

3.3 Gene Therapy 51

3.4 Gene Delivery Systems Based on Polysaccharides 53

3.5 Practical Application of Gene Delivery Systems 56

3.6 Polysaccharide-Based Nanoparticles 57

3.7 DNA Delivery 63

3.7.1 siRNA Delivery 65

3.8 Conclusion 70

4 Hydrogel-Based Gene Therapy 77
Shweta Kumari, Dipti Jena, Vedant Kumar Prajapati, Shashi Ranjan Singh and Garima Tripathi

4.1 Introduction 78

4.2 Gene Therapy 83

4.3 In Vivo Gene Therapy Using Hydrogels 86

4.4 Encapsulating Cells in Hydrogels for Gene Therapy Delivery 87

4.5 Hydrogels for Integrative Tissue Engineering and Cell Delivery 89

4.6 Biocompatible Hydrogels for Transferring Cells 91

4.7 Using Hydrogels for Gene Therapy in Tissue Engineering-Based Drug 93

4.8 Human Gene Therapy that Uses Hydrogel as an Alternative Method of Delivering Genetic Material to Patients 94

4.9 Recent Advancement in Biocompatible Hydrogel 96

4.10 Applications of Hydrogel 99

4.11 Current Hydrogels in Clinical Trials 104

4.12 Conclusions 106

5 Progress and Prospects for Non-Viral Gene Therapy 117
Shashimala Tiwari

5.1 Introduction 118

5.2 Definition 118

5.3 Technology Overview for Non-Viral Gene Delivery 119

5.4 Chemical Carriers for Gene Transfer: Establishing Effective In Vivo Gene Delivery 121

5.5 Types of Gene Delivery 122

5.6 Reduction of Immunological Responses Through Alteration of Delivery Method or DNA Structure 124

5.7 To Enable Long-Lasting Gene Expression, Self-Replicating, Tissue-Specific, and Integrating Plasmid

Expression Systems are Designed 124

5.8 Hybrid Vector Systems to Improve Transfection and Lessen Cytotoxicity 125

5.9 Vehicle Material 127

5.10 Further Effects 129

5.11 Challenges and Prospects 130

5.12 Conclusion 132

6 Nanoparticles for Tumor Gene Therapy: Recent Advances and Perspective 139
R. Shivhare, V. Sabale, A. Ingole and Neelam Jain

6.1 Introduction 140

6.2 Technologies for Gene Delivery 142

6.3 Cancer Treatment with Gene Therapy 147

6.4 Gene Therapy Using Nanotechnology 147

6.5 Challenges and Future Aspects 160

7 Effective Gene Transfer with Non-Viral Vectors 183
Anil Kumar Mavi, Sonal Gaur, Neelesh Kumar, Avanish Kumar Shrivastav, Sankha Bhattacharya,
Sateesh Belemkar, Saurabh Maru and Dhruv Kumar

7.1 Introduction 184

7.2 System Development for Delivering Genes 186

7.3 Methods for Non-Viral Vector for Delivery of Genes 186

7.4 Delivery System 203

7.5 Current Methods for Nonviral Gene Delivery: Benefits and Drawbacks 209

7.6 Current Barriers for Non-Viral Vectors 210

7.7 Possibilities for Enhancing the Non-Viral Vector Delivery System 212

7.8 Conclusion 212

7.9 Future Relevance 213

8 Utilization of Chitosan for Gene Delivery 223
Johnson Olaleye Oladele

8.1 Introduction 224

8.2 Cationic Polymers-Based Gene Delivery Systems 225

8.3 Chitosan and Its Derivatives in Gene Delivery Systems 228

8.4 Chitosan as Chemotherapeutic Drugs 234

8.5 Conclusion 236

9 Nanoparticles as Gene Vectors in Tumor Therapy 247

Efstathia Triantafyllopoulou, Orestis Kontogiannis, Nefeli Lagopati, Natassa Pippa and Maria Gazouli

9.1 Introduction 248

9.2 Polymer-Based Nanocarriers: Their Technology and Recent Advances 249

9.3 Conclusions 271

10 Progress in Non-Viral Delivery of Nucleic Acid: Advancement in Biomedical Technology 281
Anil Kumar Mavi, Manmohan Kumar, Amarjeet Singh, Mahendra Kumar Prajapati, Rakhi Khabiya, Saurabh Maru and Dhruv Kumar

10.1 Introduction 282

10.2 Physical Methods of Non-Viral Nucleic Acid Delivery System 285

10.3 Advantages and Disadvantages of Physical Transfection 296

10.4 Chemical Methods of Non-Viral Nucleic Acid Delivery System 296

10.5 Advantages and Disadvantages of Chemical Transfection 308

10.6 Cellular Barriers for Nucleic Acid Delivery Faced by Non-Viral Vectors 309

10.7 Challenges and Limitations of Non-Viral Nucleic Acid Delivery System 311

10.8 Conclusion 311

11 The Junction of Biomaterials and Gene Therapy -- Current Strategies and Future Directions 323
Ranjan Kumar Singh, Sunita Panchawat, Chennu M.M. Prasada Rao, Joohee Pradhan, Rajeswari Tanniru, Deepika Bairagee and Ajay Kumar Garg

11.1 Introduction 324

11.2 Viral Gene Therapy 327

11.3.1 Adenoviral Vectors 329

11.4 Adeno-Associated Viral Vectors 330

11.5 Non-Viral Gene Therapy 331

11.6 Recent Advances in the Development of Gene Delivery Systems 334

11.7 Development of Gene Delivery Systems 335

11.8 Viral Vectors Based on DNA for Gene Delivery Systems 336

11.9 Viral Vectors Based on RNA for Gene Delivery Systems 337

11.10 Oncolytic Viral Vectors for Gene Delivery Systems 337

11.11 Practical Application of Gene Delivery Methods 343

11.12 Conclusion 347

12 Utilization of Silk for Gene Delivery 349
Swatantra K. S. Kushwaha, Shruti Khare and Neelottama Kushwaha

12.1 Introduction 350

12.2 Dimensional Structure of Silk 350

12.3 Properties of Silk 351

12.4 Extraction of Fibroin from Silk Worm 352

12.5 Fabrication of Silk in Different Therapeutics Carriers 353

12.6 Utilization of Silk for Gene Therapy 354

12.7 Properties of Silk Fibroin as Biomaterial 355

12.8 Summary of Silk-Based Formulations for Gene Delivery 357

12.9 Examples of Some Delivery Approaches which Utilizes Silk as a Biomaterial for Gene Delivery 358

12.10 Some Highlights of Silk Fibroin 360

12.11 Conclusion 360

13 Challenges and Emerging Problems in Nanomedicine Mediated Gene Therapy 367
Shalini Bhatt, Neha Faridi, Rakshit Pathak, Vinay Deep Punetha and Mayank Punetha

13.1 Introduction 368

13.2 Why Nanomedicine Over Traditional Drugs? 369

13.3 Nanomedicine for Gene Therapy 373

13.4 Complications in Nanomedicine-Mediated Gene Therapy 384

13.5 Challenges in the Clinical Translation of Nanomedicines 391

13.6 Conclusion 396

14 Biomaterials-Based Vaccination in Cancer Therapy 417
Rishav Sharma, Rishabha Malviya and Sonali Sundram

14.1 Introduction 417

14.2 Tumor-Associated Antigens 418

14.3 Vaccine Delivery 419

14.4 Dendritic Cells 420

14.5 In Vitro Generation of Dendritic Cells 421

14.6 Usage of RNA 422

14.7 RNA-Pulsed DCs as Vaccines 422

14.8 RNA Vaccines 425

14.9 Optimization of Immunotherapy 426

14.10 Cancer Treatment Through RNA Interference 427

14.11 Conclusion 428

References 429

Index 435

Neelam Jain, PhD, holds a Doctorate in Pharmaceutics (specialization in Nanomedicine) from the Institute of Foreign Trade and Management, Moradabad, Uttar Pradesh, India. She has over 11 years of research and teaching experience and is now an associate professor at the Faculty of Pharmacy, Oriental University, Indore, India. She has been working on an array of projects relating to nanomedicine, gene therapy, nanotechnology, and pharmacology. She published more than 50 research/review papers in nanomedicine, drug delivery, and formulation technology in peer-reviewed journals and books.