Introduction to Viral Vectors and Other Delivery Methods for Gene Therapy of the Nervous System

The use of gene therapy in neuroscience research has become common place in many laboratories across the world. However, contrary to common belief, the practical application of viral or non-viral gene therapy is not as straightforward as it may seem. All too often investigators see their experiments fail due to low-quality third-party vectors or due to a lack of knowledge regarding the proper use of these tools. For example, researchers often find themselves performing experiments using the wrong methodology (e.g., using the wrong type of vector or mishandling the vector to the point where the efficacy is significantly reduced) resulting in experiments that potentially fail to accurately answer a hypothesis, or the generation of irreproducible data. Thus, it is important for investigators that seek to utilize gene therapy approaches to gain a basic understanding of how to apply this technology. This includes understanding how to appropriately design and execute an experiment, understanding various delivery vehicles (e.g., what virus to use), delivery methods (e.g., systemic versus intracranial injections), what expression system to use, and the time course involved with a particular expression system. This chapter is intended to present an overview of this fundamental knowledge, providing the researcher with a decision tree upon which to build their gene therapy experiment.