Chapter 1 - Gene Therapy Methods and Their Applications in Neurological Disorders

Abstract

Gene therapy is broadly defined as using nucleic acids as a treatment for disease, including replacing defective genes with normal ones. Gene therapy approaches to diseases of the nervous system are very important as treatments for these often-devastating disorders are limited or not available at all. Gene therapies are being tested in human clinical trials and also provide powerful research tools. A better understanding of the currently available gene therapy methods, including gene delivery vehicles, expression systems, and gene regulation tools, is critical for the success of a gene therapy project and for developing new gene therapy strategies. In this chapter, we describe viral and nonviral vectors for gene delivery into the central nervous system, including advantages, shortcomings, and applications of these vectors. We also introduce tools for regulating transgene expression, including optogenetics and Designer Receptors Exclusively Activated by Designer Drugs. We will discuss strategies of gene overexpression, gene silencing, and genome editing. We also provide examples of application of each strategy in animal models or clinical trials of neurological diseases such as lysosomal storage diseases, neurodegenerative disorders, and Duchenne muscular dystrophy. Our goal is to present an overview of methods used in gene therapy so that neurological researchers can choose the appropriate tools for research projects and for development of new gene therapies.