Poller / Barciszewski RNA Technologies in Cardiovascular Medicine and Research

1. Auflage 2008
ISBN: 978-3-540-78709-9
Verlag: Springer-Verlag
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 358 Seiten

In this book the authors review the field and explore the potential role of RNAi and other RNA technologies in cardiovascular medicine and research. They highlight the impressive recent progress but also the hurdles that still must be overcome before this promising technology is finally ready for translation and clinical use.

Autoren/Hrsg.

Poller, Wolfgang

Barciszewski, Jan

Inhaltsverzeichnis

1;Preface;5
2;Contents;9
3;Contributors;11
4;Part I MicroRNA;16
4.1;An Overview of MicroRNA;17
4.1.1;1 Introduction;18
4.1.2;2 miRNA Biogenesis;19
4.1.3;3 Biological Functions of miRNAs;19
4.1.4;4 miRNAs in Human Disease;22
4.1.5;5 Summary;25
4.1.6;References;26
4.2;MicroRNAs and Their Potential;31
4.2.1;1 The Importance of Being miRNA;32
4.2.2;2 Post-Transcriptional Regulatory Mechanisms During Cardiac Hypertrophy;32
4.2.3;3 Post-Transcriptional Regulation by miRNA;32
4.2.4;4 Transcriptional and Post-Transcriptional Regulation of miRNA;37
4.2.5;5 The Mechanism of miRNA-Target Recognition;38
4.2.6;6 miRNA in Development and Disease;39
4.2.7;7 The Diagnostic and Prognostic Potential of miRNA;43
4.2.8;8 miRNA as Therapeutic Targets;44
4.2.9;9 Concluding Remarks;44
4.2.10;References;45
4.3;miRNAs and Their Emerging Role in Cardiac Hypertrophy;49
4.3.1;1 Introduction;50
4.3.2;2 Biology of miRNAs;50
4.3.3;3 miRNAs in Cardiovascular Development;54
4.3.4;4 miRNAs in the Hypertrophic Growth Response;58
4.3.5;5 Conclusions and Future Directions;62
4.3.6;References;62
4.4;MicroRNAs and the Control of Heart Pathophysiology;67
4.4.1;1 miRNA: Biogenesis and Mechanisms of Action;67
4.4.2;2 miRNAs and Muscle Development;73
4.4.3;3 miRNAs and Heart Pathophysiology;75
4.4.4;4 Conclusion and Future Prospects;79
4.4.5;References;79
4.5;MicroRNA Systems Biology;83
4.5.1;1 Introduction;84
4.5.2;2 miRNA Regulation of Cellular Signaling Networks;85
4.5.3;3 miRNA Regulation of Gene Regulatory Networks;91
4.5.4;4 miRNA Regulation of Metabolic Networks;93
4.5.5;5 miRNA Regulation of Protein Interaction Networks;94
4.5.6;6 miRNA Regulatory Network Motifs;95
4.5.7;7 Summary;98
4.5.8;References;98
5;Part II RNA Interference;101
5.1;Targeting Viral Heart Disease by RNA Interference;103
5.1.1;1 Introduction;103
5.1.2;2 Preclinical Results of Therapeutic Antiviral RNA Interference: Focus on CVB3- Associated Disease;106
5.1.3;3 Factors That Limit Early Efficacy of Antiviral RNA Interference;111
5.1.4;4 Factors That Limit Subsequent Efficacy of Antiviral RNA Interference;113
5.1.5;5 Conclusions and Future Prospects;116
5.1.6;References;117
5.2;Design of siRNAs and shRNAs for RNA Interference: Possible Clinical Applications;123
5.2.1;1 Introduction;124
5.2.2;2 Adverse Effects of Long dsRNAs;126
5.2.3;3 siRNA Structure and Design;127
5.2.4;4 shRNAs;134
5.2.5;5 Clinical Application;139
5.2.6;6 Concluding Remark;141
5.2.7;References;142
5.3;RNA Interference and MicroRNA Modulation for the Treatment of Cardiac Disorders;145
5.3.1;1 Introduction to RNA-Based and Gene Therapeutic Strategies;146
5.3.2;2 Key Issues of Current Vector Technologies;147
5.3.3;3 RNA Interference Targeting Early Pathogenic Steps in Cardiomyopathies;151
5.3.4;4 RNA Interference to Improve Cardiac Function in Advanced Heart Failure;165
5.3.5;5 Clinical Perspectives and Unanswered Questions;173
5.3.6;References;175
5.4;Cardiac Delivery of Nucleic Acids by Transcriptional and Transductional Targeting of Adeno- Associated Viral Vectors;181
5.4.1;1 Introduction;181
5.4.2;2 Vector Systems for Cardiac Nucleic Acid Transfer;183
5.4.3;3 Transductional Targeting of AAV Vectors for Cardiac Nucleic Acid Transfer;185
5.4.4;4 Transcriptional Targeting of AAV Vectors for Cardiac Nucleic Acid Transfer;187
5.4.5;5 Application Systems for Cardiac Gene Transfer;188
5.4.6;6 Perspective;191
5.4.7;References;191
6;Part III Ribozymes;197
6.1;Characterization of Hammerhead Ribozymes Potentially Suitable for the Treatment of Hyper- Proliferative Vascular Diseases;199
6.1.1;1 Introduction;200
6.1.2;2 Hammerhead Ribozyme;200
6.1.3;3 Potential Use of HRzs as Therapeutics for Artery Restenosis;211
6.1.4;4 HRzs and Small Interfering RNAs in the Cardiovascular Field;216
6.1.5;5 Conclusion;218
6.1.6;References;218
6.2;Applications of Ribozymes and Pyrrole – Imidazole Polyamides for Cardiovascular and Renal Diseases;223
6.2.1;1 Introduction;224
6.2.2;2 Ribozymes;225
6.2.3;3 Pyrrole–Imidazole (PI) Polyamides;236
6.2.4;4 Conclusions;240
6.2.5;References;241
7;Part IV Noncoding, Aptamer and Antisense RNAs;247
7.1;Noncoding RNAs in Human Diseases;249
7.1.1;1 Noncoding RNAs;250
7.1.2;2 Functions of ncRNAs;251
7.1.3;3 NcRNAs in Human Diseases;257
7.1.4;4 Perspectives;262
7.1.5;References;263
7.2;Aptamers and siRNAs in Cardiovascular Disease;269
7.2.1;1 Introduction;270
7.2.2;2 Coagulation and Thrombosis;271
7.2.3;3 Aptamers as Anticoagulants;272
7.2.4;4 VWF Aptamers as Antiplatelet Agents;276
7.2.5;5 Aptamers and Intimal Hyperplasia;278
7.2.6;6 Potential Challenges Facing Aptamers in Cardiovascular Disease;278
7.2.7;7 siRNA Background;288
7.2.8;8 siRNA as Therapeutic Agents;289
7.2.9;9 Current Clinical Uses of siRNA;290
7.2.10;10 siRNA for the Treatment of Cardiovascular Disease;291
7.2.11;11 Potential Challenges Facing siRNA in Cardiovascular Disease;295
7.2.12;12 Conclusion;297
7.2.13;References;297
7.3;Nucleic Acid Aptamers for Cardiovascular Therapeutics;303
7.3.1;1 Nucleic Acid Aptamers;303
7.3.2;2 Therapeutic Potential of Aptamers;304
7.3.3;3 Anticoagulant and Antithrombotic Aptamers;305
7.3.4;4 Antiadhesion Aptamers;307
7.3.5;5 Antiangiogenic Aptamers and Potential for Treatment of Atherosclerosis;309
7.3.6;References;310
7.4;NFkB Decoy Oligodeoxynucleotide- Based Therapy in Cardiovascular Diseases;313
7.4.1;1 Introduction;314
7.4.2;2 Application of NF-;315
7.4.3;Decoy ODN for Cardiovascular;315
7.4.4;Diseases;315
7.4.5;3 Recent Progress in Modification of NF-;318
7.4.6;Decoy;318
7.4.7;References;320
7.5;Antisense Therapy for Restenosis Following Percutaneous Coronary Interventions;325
7.5.1;1 Introduction;326
7.5.2;2 Local Drug Delivery;329
7.5.3;3 Perflourocarbon Gas Microbubble Carriers (PGMC) for Site- Specific Drug Delivery;334
7.5.4;4 Clinical Studies with AVI-4126;335
7.5.5;5 Conclusions;336
7.5.6;References;337
7.6;Toxic RNA in Pathogenesis of Human Neuromuscular Disorders;339
7.6.1;1 Introduction;340
7.6.2;2 Properties of Transcripts Containing Microsatellite Repeats;341
7.6.3;3 Myotonic Dystrophy Type 1 and 2 (DM1 and DM2);345
7.6.4;4 Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS);352
7.6.5;5 Other Disorders Associated with Toxic RNAs;354
7.6.6;6 Toxic RNAs as Therapeutic Targets;357
7.6.7;References;361
8;Index;369