Psychiatric Applications of Viral Vectors

This chapter compares and contrasts four viral vector systems (herpes simplex 1 virus, adeno-associated virus, sindbis virus, and lentivirus), best suited for gene transfer into the brain and describes the basic strategies where viral-mediated gene transfer has proven useful. The ideal viral vector for psychiatric research in animals, and eventually for treatments of humans, must have good neurotropism, cause little or no toxicity, and express the target protein(s) for extended periods of time. Viral vectors expressing the transcription factor, cAMP-response-element binding protein (CREB) or a dominant-negative mutant form of CREB (mCREB) affect behavior in rodent models ranging from depression to anxiety to drug dependence. The final discussion outlines novel uses and improvements to vector technology and describes current obstacles preventing viral vectors from becoming clinically viable. Obstacles to a clinically viable gene therapy include finding good targets, designing better vectors, controlling expression, and safety issues.