Viral Vectors for Treating Diseases of the

Gene therapy offers considerable potential for the treatment of various incurable diseases of the nervous system. This volume describes a number of different viral vectors developed for achieving high efficiency gene delivery to the brain. Vectors described include those based on adenovirus, adeno-associated virus, Herpes Simplex Virus, lentivirus, and other retroviruses. It also discusses the potential application of such viruses in treating brain tumors, Parkinson's disease, and other diseases of the nervous system. * Provides up-to-date account of gene therapy approaches for incurable neurological disorders * Describes a range of gene delivery methods based on different viruses

CONTRIBUTORS

ix

SECTION I VIRUS VECTORS FOR USE IN THE CENTRAL NERVOUS SYSTEM

Nonneurotropic Adenovirus: A Vector for Gene Transfer to the Brain and Gene Therapy of Neurological Disorders

PEDRO R. LOWENSTEIN, DONATA SUWELACK, JINWEI HU, XIANPENG YU, MAXIMILIANO JIMENEZ-OALMARONI, SHYAM GOVERDHANA, AND MARIA G. CASTRO

I. Introduction: Some History and Other Vectors

3

(4)

II. The Vector System

7

(2)

III. Developments in the Use of Adenovirus Recombinants as Vectors

9

(30)

IV. Adenoviral Recombinant Vectors: Applications to Basic Neuroscience

39

(5)

V. Adenoviral Recombinant Vectors: Applications to Neurological Gene Therapy

44

(2)

VI. Immune Responses to Recombinant Adenoviral Vectors Delivered into the Brain

46

(2)

VII. Summary: Targeting the Brain with Adenovirus-Derived Vectors

48

(4)

References

52

(13)

Adeno-Associated Viral Vectors

E. LEHTONEN AND L. TENENBAUM

I. Biology of Adeno Associated Virus and Its Recombinant Vectors

65

(9)

II. AAV Vector Production

74

(3)

III. Recombinant AAV-Mediated Transduction in the CNS

77

(5)

IV. Factors Limiting Efficient Transduction

82

(4)

V. New Vectors

86

(1)

VI. Regulation of Transgene Expression

87

(1)

VII. Biosafety

88

(2)

References

90

(9)

Problems in the Use of Herpes Simplex Virus as a Vector

LAWRENCE T. FELDMAN

I. Introduction

99

(1)

II. General Aspects of Lytic Cycle Replication and Latent Infections of Neurons in Vivo

100

(2)

III. Reducing Cytotoxicity of the Virus: The Gene Deletion Approach

102

(1)

IV. Reducing Cytotoxicity of the Virus: The Amplicon Approach

103

(1)

V. The Problem of Long-Term Expression during HSV Latency

104

(2)

References

106

(5)

Lentiviral Vectors

JOHAN JAKOBSSON, CECILIA ERICSON, NINA ROSENQVIST, AND CECILIA LUNDBERG

I. Introduction

111

(1)

II. Lentiviral Vectors

111

(3)

III. Direct Injection of Lentiviral Vectors

114

(1)

IV. Ex Vivo Gene Transfer Using Lentiviral Vectors

115

(3)

V. Concluding Remarks

118

(1)

References

119

(4)

Retroviral Vectors for Gene Delivery to Neural Precursor Cells

RYOICHIRO KAGEYAMA, HIROMI HIRATA, AND JUN HATAKEYAMA

I. Introduction

123

(1)

II. Overview of Retrovirus

124

(6)

III. Generation of Recombinant Retroviral Vectors

130

(8)

IV. Gene Delivery to the Nervous System by Retroviral Vectors

138

(7)

References

145

(6)

SECTION II GENE THERAPY WITH VIRUS VECTORS FOR SPECIFIC DISEASES OF THE NERVOUS SYSTEM

The Principles of Molecular Therapies for Glioblastoma

GEORGE KARPATI AND JOSEPHINE NALBANTOGLU

I. Introduction

151

(1)

II. Review

151

(7)

References

158

(7)

Oncolytic Herpes Simplex Virus for Tumor Therapy

JENNIFER C.C. HU AND ROBERT S. COFFIN

I. Introduction

165

(2)

II. Advantages of Oncolytic Cancer Therapy

167

(1)

III. Advantages of HSV as on Oncolytic Agent

167

(1)

IV. Attenuation of HSV to Provide Tumor-Selective Replication

168

(3)

V. Effects of Preexisting Immunity to HSV

171

(1)

VI. Effects of the Immune Response in Enhancing Tumor Therapy

171

(1)

VII. Clinical Experience with Oncolytic HSV

172

(1)

VIII. Improving Oncolytic HSV

173

(4)

IX. Conclusions

177

(1)

References

178

(7)

Recombinant Retrovirus Vectors for Treatment of Malignant Brain Tumors

NIKOLAI G. RAINOV AND CHRISTOF M. KRAMM

I. Introduction

185

(1)

II. Properties of Retrovirus Vectors and Virus Producer Cells

186

(3)

III. RV-Mediated Brain Tumor Therapy in Animal Models

189

(2)

IV. Clinical Studies with RV Vectors

191

(6)

IX. Conclusions

197

(1)

References

198

(7)

Adeno-Associated Viral Vectors for Parkinson's Disease

SHIN-ICHI MURAMATSU, LIJUN WANG, KÜNIHIKO IKEGUCHI, KEN-ICHT FUJIMOTO, IMAHARU NAKANO, TAKASHI OKADA, HIROAKI MIZUKAMI, YUTAKA HANAZONO, AKIHIRO KUME, IMAHARU NAKANO, AND KEIYA OZAWA

I. Introduction

205

(1)

II. Recombinant Adeno Associated Viral Vector

206

(1)

III Restoration of DA Synthesis in the Striatum

207

(6)

IV. Neuroprotection by GDNF Gene Delivery

213

(3)

V. Conclusions

216

(2)

References

218

(5)

Herpes Simplex Virus Vectors for Parkinson's Disease

DAVID S. LATCHMAN

I. Introduction

223

(1)

II. Gene Therapy and Parkinson's Disease

224

(1)

III. Therapeutic Genes for Parkinson's Disease

224

(2)

IV. Genetics of Parkinson's Disease

226

(2)

V. Gene Delivery to the Nervous System

228

(1)

VI. HSV as a Vector

228

(7)

VII. HSV as a Vector for Parkinson's Disease

235

(2)

VIII. Conclusion

237

(1)

References

238

(5)

Gene Therapy for Stroke

K. ABE AND W.R. ZHANG

I. Introduction

243

(1)

II. Neurotrophic Factors

244

(5)

III. Application of Neurotrophic Factors

249

(4)

IV. Gene Therapy

253

(6)

V. Stem Cells

259

(4)

References

263

(8)

Gene Therapy for Mucopolysaccharidosis

ASSUMPCIO BOSCH AND JEAN MICHEL HEARD

I. Definition and General Considerations on Lysosomal Storage Diseases

271

(2)

II. Addressing Lysosomal Enzymes to the Lysosomes: Enzyme Replacement Therapy

273

(4)

III. Mucopolysaccharidosis

277

(1)

IV. Animal Models for Mucopolysaccharidosis

278

(1)

V. Treatment Strategies for Mucopolysaccharidosis

279

(9)

VI. Perspectives

288

(1)

References

289

(8)

INDEX

297

(22)

CONTENTS OF RECENT VOLUMES

319

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Viral Vectors for Treating Diseases of the Nervous System

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