Non-Viral Vectorsfor Gene Therapy

Second Editio nPart I ILeaf Huan g

Mien-Chie Hun g

Ernst Wagner

Contributors

xii iPreface

xvi i

1 NAKED DNA, OLIGONUCLEOTIDE AN DPHYSICAL METHOD S

1 The Mechanism of Naked DNA Uptakeand Expression

3Jon A. Wolff and Vladimir Budke r

I . Overview of Hepatocyte Delivery

511 . Transport of Nucleic Acids from Injection

Site to Liver

6III. Extravastion of Injected Nucleic Acid

7IV. Cytoplasmic Entry

8V. Entry of Nucleic Acid into the Nucleus

1 1VI. Uptake of Naked DNA by Muscle Cells Afte r

Direct Intramuscular Injection

1 3VII. Delivery of Naked DNA to Muscle via

Intravascular Routes

1 5VIII. Conclusions

1 6References

1 7

2 Targeted Delivery of Therapeutic Oligonucleotides t o

Pulmonary Circulation

2 1Annette Wilson, Fengtian He, Jiang Li, Zheng Ma,Bruce Pitt, and Song Li

1 . Introduction

2 2ll . Chemistry of Oligodeoxynucleotides

2 3111 . Pulmonary Physiology that Affects

Endothelium Targeting

2 7IV. Lipid Vectors for Pulmonary

Oligonucleotide Delivery

32

V. Conclusion

3 5References

35

3 Naked DNA for Liver Gene Transfer

43Feng Liu and Pradeep Tyag i

I. Introduction

4 4II. Liver Gene Transfer by Naked DNA Injection

4 6III. Liver Gene Transfer by Electroporation

4 7IV. Liver Gene Transfer by the Gene Gun

5 2V. Liver Gene Transfer by Injection via Portal and

Efferent Vessels

5 5VI. Liver Gene Transfer b y

Systemic Administration

5 6VII. Conclusion

6 0References

6 1

4 Hydrodynamic Delivery

65Mohammed S . Al-Dosari, Joseph E . Knapp, and Dexi Liu

I. Introduction

66II. Principles of Hydrodynamic Delivery

6 6III. Hydrodynamics-Based Procedures

6 9IV. Applications of Hydrodynamic Delivery

7 1V. Conclusion and Future Perspectives

7 4References

7 6

5 Electric Pulse-Mediated Gene Delivery to Variou s

Animal Tissues

83Lluis M . Mir, Pernille H. Moller, Franck Andre, andJulie Gehl

I. Introduction

84II. Basic Principles of Electro Gene Transfer

84III. Electrodes for In Vivo Gene Delivery

8 9IV. Preclinical Studies

9 0V. Perspectives for Clinical Use of Electro

Gene Transfer

10 3VI. Conclusion

10 3References

104

2 GENE REGULATION

6 In Vivo Application of RNA Interference : From Functiona lGenomics to Therapeutics

11 7Patrick Y. Lu, Frank Xie, and Martin C. Woodl e

1 . Introduction

11 811 . Delivering Short Interfering RNA (siRNA) In Vivo

12 2

III . In Vivo siRNA Applications

13 1References

138

7 A Novel Gene Expression System : Non-Viral Gene Transfe rfor Hemophilia as Model Systems

143Carol H. Miao

1 . Introduction

144II . Gene Expression Systems

14511I . Non-Viral Gene Transfer for Hemophilia a s

Model Systems

163IV. Conclusions and Future Prospects

17 0References

17 1

8 Site-Specific Integration with g5C31 Integrase fo rProlonged'Expression of Therapeutic Genes

17 9Daniel S . Ginsburg and Michele P . Calo s

I. Introduction

18 0II. OC31 Integrase

18 1III. OC31 Integrase Function in Mammalian Cells

18 2IV. Conclusions

18 5References

186

9 Sleeping Beauty Transposon-Mediated Gene Therapy fo rProlonged Expression

189Perry B. Hackett, Stephen C . Ekker, David A. Largaespada,and R. Scott Mclvor

L Introduction

19 011 . The Sleeping Beauty Transposon System

195111 . Applications of Sleeping Beauty Transposons for

Gene Therapy

211

IV. Future Directions

22 0References

223

3 ANIMAL MODEL AND CLINICAL STUDY

10 Cancer-Specific Gene Therapy

235Hui-Wen Lo, Chi-Ping Day, and Mien-Chie Hung

I. Introduction

23 6II. Development of Cancer-Specific Vectors

23 7III. Conclusion

246References

24 7

11 DNA Vaccine

257Zhengrong Cu i

I. Introduction

258II. Composition of DNA Vaccine

259III. Advantages and Disadvantages of

DNA Vaccine

260IV. Mechanisms of Immune Induction from

DNA Vaccine

26 1V. The Immunostimulatory Activity of CpG Motif

26 4VI. Route of Administration

266VII. Immunology of the Immune Responses fro m

DNA Vaccine

268VIII. Clinical Trials of DNA Vaccines

27 1IX. Safety Issues

28 0X. Conclusion

283References

28 3

12 Airway Gene Therapy

29 1Jane C . Davies and Eric W. F. W Alto n

I. Routes of Administration forAirway Expression

29 2II. Barriers to Gene Transfer and Expression

293III. Novel Strategies to Increase the Uptake of

Gene Transfer Agents

29 6IV. Extending the Duration of Expression

29 8V. Limiting the Host Immune Response

298

VI . Specific Lung Diseases : Progress Toward

Clinical Application

299

V 11 . Conclusions

30 7References

30 7

13 Non-Viral Vector as Vaccine Carrier

31 5Weihsu Claire Chen and Leaf Huan g

1 . Introduction

31 6

[I . Potential Disadvantages of Naked

DNA Immunization

31 8

III. Vaccine Adjuvants and Formulation

31 8

IV. Liposome-Mediated Genetic Vaccination

31 9

V. Liposome-Mediated Peptide Vaccination

323

VI. Liposome-Mediated RecombinantProtein Vaccination

32 9Vll . Conclusion

33 3References

33 3

14 Non-Viral Vectors for Gene Therapy : Clinical Trials inCardiovascular Disease

339Pinak B. Shah and Douglas W . Losordo

I. Introduction

34 0II. Therapeutic Angiogenesis

34 1III. Delivery of Angiogenic Cytokines

34 3IV. Clinical Trials of Non-viral Gene

Therapy for Therapeutic Angiogenesis i nCardiovascular Disease

345V. Issues in Clinical Trial Design in Gene Therapy fo r

Cardiovascular Disease

354VI. Safety Concerns Regarding Gene Therapy fo r

Ischemic Vascular Disease

35 5V11 . Conclusion

35 6References

356

Index

363