Non-Viral Vectorsfor Gene TherapySecond Editio nPartLeaf Huan g

Mien-Chie Hun g

Ernst Wagner

Contributors

xii iPreface

xvi i

1 BASIC CONCEPTS

1 Recent Advances in Non-viral Gene Delivery

3Christine C. Conwell and Leaf Huan g

I. Introduction

4II. Cationic Lipids

4III. Cationic Polymers

6IV. Triggered Release

9V. Physical Delivery Methods for Naked DNA

1 1VI. Prospects

1 5References

1 5

2 Barriers to Gene Delivery Using Synthetic Vectors

1 9Martin L. Read, Ann Logan, and Leonard W. Seymour

I. Introduction

20II. Extracellular Barriers

2 1III. Intracellular Barriers

26IV. Conclusions

40References

4 1

3 Pharmacokinetics of Plasmid DNA-Based Non-vira lGene Medicine

4 7Makiya Nishikawa, Yoshinobu Takakura, an dMitsuru Hashida

I. Introduction

4 8II. How to Trace Plasmid DNA In Vivo

5 0III. Pharmacokinetic Features of Naked Plasmid

DNA After Intravascular Injection

5 2IV. Pharmacokinetic Features of Plasmid DNA/Non-viral Vecto r

Complex After Intravenous Injection

5 6V. Pharmacokinetic Features After Tissue Injection

61

VI. Conclusion

62References

6 2

2 CATIONIC LIPOSOME S

4 What Role Can Chemistry Play in Cationic Liposome -Based Gene Therapy Research Today?

7 1Kostas Kostarelos and Andrew D. Miller

I. Introduction

7 2II. AB Core Particles

7 4III. ABD Particles

8 9IV. ABC Particles

9 7V. ABCD Particles

10 3VI. The Future Role of Chemistry-B, C, and D

Layer Innovations

10 6VII. Main Abbreviations

10 8References

110

5 Lipoplex Structures and Their DistinctCellular Pathways

119Kai Ewert, Heather M. Evans, Ayesha Ahmad,Nelle L . Slack, Alison J . Lin, Ana Martin-Herranz ,and Cyrus R . Safinya

I. Introduction

12 0II. Formation, Structures, and Stability of

CL-DNA Complexes

12 2III. Structure-Transfection Efficiency Relationships o f

CL-DNA Complexes

12 8IV. PEOylated CL-DNA Complexes : Surface Functionalization

and Distinct DNA-DNA Interaction Regimes

142V. Conclusion

147VI. Future Directions

14 7VIl . Main Abbreviations

149References

150

6 "Diffusible-PEG-Lipid Stabilized Plasmi dLipid Particles"

15 7Ian MacLachlan and Pieter Culli s

I. Introduction

15 8II. Properties of a Plasmid Delivery System for the Treatment o f

Systemic Disease

158

III. Methods of Encapsulating Plasmid DNA

16 6IV. Pharmacology of Encapsulated Plasmid DNA

17 3V. Conclusion

18 2References

18 3

7 Toxicity of Cationic Lipid-DNA Complexes

189Nelson S . Yew and Ronald K . Scheule

I. Introduction

19 0II. Acute Toxicity After Intrapulmonary Delivery

19 1III. Biodistribution of Cationic Lipid-DNA Complexe s

After Intravenous Delivery

194IV. Acute Toxicity After Intravenous Delivery

195V. Role of Immunostimulatory CpG Motifs in

Cationic Lipid-DNA Toxicity

19 6VI. Modifying the Plasmid DNA Vector to Decrease th e

CpG Response

19 9VII. Other Approaches to Reduce the Toxicity o f

Cationic Lipid-DNA Complexes

205VIII. Summary

20 9References

209

3 CATIONIC POLYMERS

8 Polyethylenimine (PEI)

21 7Barbara Demeneix and Jean-Paul Behr

I. Mechanism of Gene Delivery

21 8II. Transfection of Cells in Culture

22 2III. In Vivo Gene Delivery

22 4References

22 7

9 Pluronic Block Copolymers for Gene Delivery

23 1Alexander Kabanov, Jian Zhu, and Valery Alakho v

I. Introduction

23 2II. Pluronic Block Copolymers: The Structur e

and Nomenclature

234III. Synthesis and Purification of Pluroni c

Block Copolymers

23 6IV. Micellization, Solubilization, and Formation of Gels

236V. Biological Activities of Pluronic

Block Copolymers

239

VI. Summary of Applications of Pluronic i nGene Delivery

24 0VII. Effects of Pluronic Block Copolymers in Vira l

Gene Delivery

24 0VIII. Pluronic Block Copolymers as Adjuvants for

Non-Viral Vectors

24 2IX. Pluronic-Polycation Graft/Block Copolymers for

Gene Delivery

243X. Effects of Pluronic Block Copolymers on Gen e

Transfer Using Naked DNA

246XI. Possible Mechanisms of Pluronic Effects o n

Gene Delivery

24 8XII. Conclusion

25 0XIII. Main Abbreviations

250References

25 1

10 Terplex Gene Delivery System

263Sung Wan Kim

I. Polymeric Gene Delivery Systems

264II. Design and Characterization of Terplex

26 6III. In Vitro Vascular Cell Transfection

26 7IV. Terplex/DNA for Myocardial Transfection

26 9References

27 3

11 Design of Polyphosphoester-DNA Nanoparticles fo r

Non-Viral Gene Delivery

275Hai-Quan Mao and Kam W. Leon g

I. Introduction

27 6II. Synthesis and Structures of PPE and PPA

Gene Carriers

28 1III. Polycationic PPAs-Structure-Property Relationship : DNA

Compaction Capacity and Gen eTransfection Efficiency

28 7IV. Polycationic PPEs-Effect of Sidechain Structure on

Degradation of Carrier, DNA Release Rate, an dTransfection Efficiency

29 5V. PPE with a Charge Center in the Backbone

299VI. Summary

30 1References

302

12 Development of HVJ Envelope Vector and Its Applicatio nto Gene Therapy

307Yasufumi Kaneda, Seiji Yamamoto, and Toshihiro Nakajim a

I. Introduction

30 8II. Preparation of HVJ Envelope Vector

31 1III. Gene Transfer to Cultured Cells Using HV J

Envelope Vector

31 3IV. Gene Transfer In Vivo Using

HVJ Envelope Vector

31 5V. Gene Therapy for Hearing Impairment Using

HVJ Envelope Vector

31 8VI. Approaches to Cancer Gene Therapy Using

HVJ Envelope Vector

32 0VII. Toward the Clinical Trial

326VIII. Main Abbreviations

32 8References

32 8

13 Targeting of Polyplexes: Toward Synthetic VirusVector Systems

33 3Ernst Wagner, Carsten Culmsee, and Sabine Boeckl e

1 . Introduction

334II. Extracellular Delivery : Tissue and

Cell Targeting

33 4III. Cellular Uptake and Intracellular Trafficking

33 9IV. In Vivo Administration of Polyplexes

and Applications

34 1V. Optimizing Polyplexes Toward

Synthetic Viruses

34 5VI. Conclusions

347VII. Main Abbreviations

34 7References

348

Index

355