Helper virus-free herpes simplex virus-1 plasmid vectors for gene therapy of Parkinson's disease and other neurological disorders.
Vectors based on herpes simplex virus type 1 (HSV-1) have potential for gene therapy of neurological disorders. HSV-1 plasmid vectors (amplicons) contain only approximately 1% of the 150-kb HSV-1 genome and have been packaged into virus particles by using a helper virus. We have demonstrated that HSV-1 plasmid vectors which express tyrosine hydroxylase can cause long-term biochemical and behavioral recovery in the 6-hydroxydopamine rat model of Parkinson's disease. Furthermore, we and others have used HSV-1 plasmid vectors which express a wide range of genes that affect neuronal physiology. Because of the pathogenicity of the HSV-1 helper virus, however, the use of this vector system has been limited to studies in animal models or primary cultures of neural cells. Thus, to increase the safety of HSV-1 plasmid vectors, we recently developed a helper virus-free packaging system that may facilitate studies on neuronal physiology and potential therapeutic applications.
Geller
A I
AI
Division of Endocrinology, Children's Hospital, Boston, Massachusetts 02115, USA.
Yu
L
L
Wang
Y
Y
Fraefel
C
C
D000818:Animals; D015316:Genetic Therapy; D005822:Genetic Vectors; D006378:Helper Viruses / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D009422:Nervous System Diseases / Q000628:therapy*; D010300:Parkinson Disease / Q000628:therapy*; D010957:Plasmids