Challenges in Delivery of Therapeutic Genomics and Proteomics (eBook)

Front Cover 1
Challenges in Delivery of Therapeutic Genomics and Proteomics 4
Copyright Page 5
Contents 6
Preface 10
List of Contributors 14
Chapter 1 The Cell 16
1.1 Introduction 16
1.2 Genes, Chromosomes, DNA, and RNA 20
1.3 Transcription 28
1.4 Translation 30
1.5 Transcriptional Control of Gene Expression 33
1.6 Cell Communication or Biosignaling 33
1.7 Cell–Cell Adhesion and Extracellular Matrix 39
1.8 Cell Cycle 40
1.9 Transporters 47
1.10 Conclusion 52
Chapter 2 Challenges and Opportunities in Gene Delivery 60
2.1 Introduction 60
2.2 Barriers to Gene Delivery 64
2.3 Extracellular Barriers 64
2.4 Intracellular Barriers for Naked DNA and DNA Delivery Systems 76
2.5 Biological and Immune Response as Barriers (Especially for Viral Vectors) 86
2.6 Scale-up Barriers and FDA Approval 87
2.7 Conclusion 87
Chapter 3 Gene Delivery Using Physical Methods 98
3.1 Introduction 98
3.2 Naked DNA Delivery 100
3.3 Electroporation 103
3.4 Hydrodynamic Gene Therapy 108
3.5 Particle Bombardment Using Gene Gun 112
3.6 Microinjection 115
3.7 Sonoporation-Ultrasound-Mediated Gene Delivery 116
3.8 Iontophoresis 120
3.9 Magnetofection 121
3.10 Laser Beam Gene Transduction 123
3.11 Impalefection 124
3.12 Conclusion 126
Chapter 4 Gene Delivery Using Chemical Methods 142
4.1 Introduction 142
4.2 Polymeric Vectors 143
4.3 Lipidic Vectors 167
4.4 Lipid Polymer Hybrid Systems or Lipopolymers 182
4.5 Peptides 183
4.6 Dendrimers 187
4.7 Biopolymers 192
4.8 Conclusion 198
Chapter 5 Gene Delivery Using Viral Vectors 222
5.1 Introduction 222
5.2 Adenovirus 223
5.3 Adeno-Associated Virus 240
5.4 Retrovirus 249
5.5 Herpes Simplex Virus 259
5.6 Other Viral Vectors 266
5.7 Immune Response to Viral Vectors 270
5.8 Biodistribution of Viral Gene Delivery Systems 271
5.9 Conclusion 272
Chapter 6 Applications of Gene Therapy 286
6.1 Gene Therapy 286
6.2 DNA Vaccination 290
6.3 Applications of Gene Therapy in Cancer 294
6.4 Applications of Gene Therapy in Cystic Fibrosis 304
6.5 Applications of Gene Therapy in Cardiovascular Diseases 307
6.6 Applications of Gene Therapy in Kidney Diseases 310
6.7 Applications of Gene Therapy in Gaucher Disease 314
6.8 Applications of Gene Therapy in Hemophilia 316
6.9 Conclusion 318
Chapter 7 Antisense Oligonucleotides and RNA Interference 340
7.1 Introduction 340
7.2 The Evolution of Antisense Drug Technology 341
7.3 Strategies of Transcriptional Arrest 349
7.4 Barriers to Oligonucleotide and siRNA Delivery 350
7.5 Molecular Mechanisms of AS ODN Interactions 355
7.6 Types of Antisense Agents 359
7.7 Pharmacokinetics and Pharmacodynamics 365
7.8 Formulation Considerations for Antisense Drug Delivery 368
7.9 Applications of Antisense Drugs 377
7.10 Benefits of Antisense Drugs in Therapeutics 380
7.11 Regulatory Aspects and Guidelines for Targeted siRNA Delivery 381
7.12 Patent Trends 383
7.13 Future Directions 384
Chapter 8 Proteomics 402
8.1 Introduction 402
8.2 Changing Requirements of Proteins and Peptides Delivery 405
8.3 New Drug Delivery Systems for Proteins and Peptides 409
8.4 Barriers to Protein and Peptide Absorption in the Gastrointestinal Tract 412
8.5 Physical Biochemistry of Proteins and Peptides 420
8.6 Protein and Peptide Synthesis 424
8.7 Protein Purification, Characterization, and Methods of Analysis for Proteins 428
8.8 Pharmacokinetics of Proteins 436
8.9 Regulatory Perspectives of Protein and Peptide Drug Development 438
8.10 Conclusion 439
Chapter 9 Protein and Peptide Delivery through Respiratory Pathway 444
9.1 Introduction 444
9.2 Respiratory System 444
9.3 Biophysical Issues in Peptide Drug Delivery 445
9.4 Pharmaceutical Issues in Peptide Drug Delivery 453
9.5 Intranasal Delivery of Peptides and Proteins 454
9.6 Delivery of Proteins and Peptides by Inhalation 474
9.7 Conclusion 482
Chapter 10 Oral Delivery of Proteins and Peptides: Concepts and Applications 496
10.1 Introduction 496
10.2 Anatomy and Physiology of Oral Mucosa 497
10.3 Transport Mechanisms in the GI Tract 502
10.4 Barriers to Protein Absorption 505
10.5 Factors Affecting Peptides and Proteins Absorption 508
10.6 Approaches to Improve Oral Protein and Peptide Delivery 510
10.7 Technique for Oral Absorption Studies 528
10.8 Strategic Use of Oral Route for Immunization 531
10.9 Conclusion 532
Chapter 11 Parenteral Delivery of Peptides and Proteins 546
11.1 Introduction 546
11.2 Pharmacological Considerations of P/P Drugs 548
11.3 Techniques for Stabilizing Aqueous P/P Formulation 558
11.4 Polymers Used in Parenteral Delivery of P/P 565
11.5 Parenteral Delivery Systems for P/P 568
11.6 New Advances in the Parenteral Administration of P/P 594
11.7 Conclusion 609
Chapter 12 Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal 638
12.1 Transdermal Delivery of Proteins and Peptides 638
12.2 Topical Delivery of Proteins and Peptides 660
12.3 Intrauterine Delivery of Proteins and Peptides 663
12.4 Rectal Delivery of Proteins and Peptides 666
12.5 Conclusion 674