Effect of immunity on gene delivery into anterior horn motor neurons by live attenuated herpes simplex virus vector

Efficient and prolonged foreign gene expression has been demonstrated in th e bilateral anterior horn motor neurons of the spinal cord by intramuscular inoculation with attenuated herpes simplex virus (HSV) expressing latency associated transcript promoter-driven beta -galactosidase ()beta H1). To ex amine the effect of immunity on the gene delivery, beta H1 was applied in r ats immunized subcutaneously or intramuscularly with the parent HF strain. Rats were immunized subcutaneously with HF strain and 28 days later when th e high antibody titer was maintained, beta H1 was inoculated into the right gastrocnemius muscle. Second, 35 days after inoculation with HF strain int o the right gastrocnemius muscle, beta H1 was inoculated at the same site. In both ways of immunization, immunity did not abolish or prevent the trans gene expression in the anterior horn motor neurons, but attenuated the rang e and the number of the beta -galactosidase-positive neurons from about 85% to 50-65% on 28 days after inoculation with beta H1. However, beta -galact osidase activity was observed in a wide range of the bilateral anterior hor n motor neurons without significant pathological changes. These findings su pport the feasibility of the attenuated HSV vector in gene delivery into th e central nervous system, even in the presence of immunity.