Gene Therapy for Neurological Disorders, Softcover reprint of the original 1st ed. 2016 Methods and Protocols Methods in Molecular Biology Series, Vol. 1382

This volume provides a clear and detailed roadmap of how to design and execute a gene therapy experiment in order to obtain consistent results. Chapters in this book disseminate bits of unknown information that are important to consider during the course of experimentation and will answer questions such as: What delivery vehicle do you use?; How will you ensure that your vector retains stability?; What expression system best fits your needs?; What route will you choose to deliver your gene therapy agent?; How will you model the neurodegenerative disorder that you aim to investigate and what are the proven methods to treat these disorders in preclinical models? Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols and tips on troubleshooting and avoiding known pitfalls.

Authoritative and thorough, Gene Therapy for Neurological Disorders: Methods and Protocols, is a compilation of protocols and instructive chapters intended to give researchers, clinicians, and students of all levels, a foundation upon which future gene therapy experiments can be designed.

Part I Introduction

1.Introduction to Viral Vectors and Other Delivery Methods for Gene Therapy of the Nervous System
Frederic P. Manfredsson

Part II Expression Cassettes       

2. Delivering Transgenic DNA Exceeding the Carrying Capacity of AAV Vectors
Matthew L. Hirsch, Sonya J. Wolfe, and R. J. Samulski

3. Expression of Multiple Functional RNAs or Proteins from One Viral Vector
Tomas Björklund

4. Regulated Gene Therapy
Ludivine Breger, Erika Elgstrand Wettergren, Luis Quintino, and Cecilia Lundberg

5. Design of shRNA and miRNA for Delivery to the CNS
Gabriela Toro and Christian Mueller

6. Tissue Specific Promoters in the CNS
Sebastian Kügler

Part III Viral Vector Production

7. Small Scale Recombinant Adeno-Associated Virus Purification
Corinna Burger and Kevin Nash

8. Lentivirus Production and Purification
Matthew J. Benskey and Frederic P. Manfredsson

9. Viral Vector Production: Adenovirus
Julius W. Kim, Ramin A. Morshed, J. Robert Kane, Brenda Auffinger, Jian Qiao, and Maciej S. Lesniak

Part IV Viral Vector Tropism

10. Controlling AAV Tropism in the Nervous System with Natural and Engineered Capsids
Michael J. Castle, Heikki T. Turunen, Luk H. Vandenberghe, and John H. Wolfe

11. Altering Tropism of rAAV by Directed Evolution
Damien Marsic and Sergei Zolotukhin

12. Altering Entry Site Preference of Lentiviral Vectors into Neuronal Cells by Pseudotyping with Envelope Glycoproteins
Kenta Kobayashi, Shigeki Kato, Ken0ichi Inoue, Masahiko Takada, and Kazuto Kobayashi

13. Directed Evolution of Adenoviruses
Jason G. Smith

Part V Delivery Methods

14. Intraparenchymal Stereotaxic Delivery of rAAV and Special Considerations in Vector Handling
Matthew J. Benskey and Frederic P. Manfredsson

15. MRI-Guided Delivery of Viral Vectors
Ernesto A. Salegio, John Bringas, Krystof S. Bankiewicz

16. Systemic Gene Therapy for Targeting the CNS
Sara E. Gombash and Kevin D. Foust

17. Widespread Neuronal Transduction of the Rodent CNS via Neonatal Viral Injection
Ji-Yoen Kim, Stacy D. Grunke, and Joanna L. Jankowsky

18. AAV-Mediated Gene Transfer to Dorsal Root Ganglion
Hongwei Yu, Gregory Fischer, and Quinn H. Hogan

19. Gene Therapy of the Peripheral Nervous System: The Enteric Nervous System
Matthew J. Benskey and Frederic P. Manfredsson

20. Gene Therapy of the Peripheral Nervous System: Celiac Ganglia

21. Convection Enhanced Delivery of Recombinant Adeno-Associated Virus into the Mouse Brain
Kevin R. Nash and Marcia N. Gordon

22. Non-Viral Gene Therapy of the Nervous System: Electroporation
XueFeng Ding and Ming Fan

23. Non-Viral, Lipid-Mediated DNA and mRNA Gene Therapy of the Central Nervous System (CNS): Chemical-Based Transfection
James G. Hecker

24. Ex Vivo Gene Therapy Using Human Mesenchymal Stem Cells to Deliver Growth Factors in the Skeletal Muscle of a Familial ALS Rat Model
Masatoshi Suzuki and Clive N. Svendsen

Part VI Gene-Therapy Based Modeling of Neurodegenerative Disorders

25. Gene Therapy Models of Alzheimer’s Disease and Other Dementias
Benjamin Combs, Andrew Kneynsberg, and Nicholas M. Kanaan

26. Viral Vector-Based Modeling of Neurodegenerative Disorders: Parkinson’s Disease
D. Luke Fischer, Sara E. Gombash, Christopher J. Kemp, Frederic P. Manfredsson, Nicole K. Polinski, Megan F. Duffy, and Caryl E. Sortwell

27. Gene Therapy-Based Modeling of Neurodegenerative Disorders: Huntington's Disease
Deborah Young

Part VII Gene-Therapy for the Treatment of Neurological Disorders

28. Gene Therapy for the Treatment of Neurological Disorders: Amyotrophic Lateral Sclerosis
Zachary T. Mceachin, Anthony Donsante, and Nicholas Boulis

29. Stereotaxic Surgical Targeting of the Non-Human Primate Causate and Putamen: Gene Therapy for Huntington’s Disease
Jodi L. McBride and Randall L. Clark

30. Gene-Therapy for the Treatment of Neurological Disorders: Metabolic Disorders
Dominic J. Gessler and Guangping Gao

31. Gene Therapy for the Treatment of Neurological Disorders: Central Nervous System Neoplasms
Neha Kamran, Marianela Candolfi, Gregory J. Baker, Mariela Moreno Ayala, Marta Dzaman, Pedro R. Lowenstein, and Maria G. Castro

Part VIII Clinical Trials

32. AAV2-Neurturin for Parkinson’s Disease: What Lessons Have We Learned?
Jeffrey H. Kordower

Includes cutting-edge methods and protocols

Provides step-by-step detail essential for reproducible results

Contains key notes and implementation advice from the experts