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 the 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 (betaH1). To examine the effect of immunity on the gene delivery, betaH1 was applied in rats immunized subcutaneously or intramuscularly with the parent HF strain. Rats were immunized subcutaneously with HF strain and 28 days later when the high antibody titer was maintained, betaH1 was inoculated into the right gastrocnemius muscle. Second, 35 days after inoculation with HF strain into the right gastrocnemius muscle, betaH1 was inoculated at the same site. In both ways of immunization, immunity did not abolish or prevent the transgene expression in the anterior horn motor neurons, but attenuated the range and the number of the beta-galactosidase-positive neurons from about 85% to 50-65% on 28 days after inoculation with betaH1. However, beta-galactosidase activity was observed in a wide range of the bilateral anterior horn motor neurons without significant pathological changes. These findings support the feasibility of the attenuated HSV vector in gene delivery into the central nervous system, even in the presence of immunity.
Kamiyama
H
H
Department of Neurosurgery, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan.
Kurimoto
M
M
Yamamura
J
J
Uwano
T
T
Hirashima
Y
Y
Kurokawa
M
M
Endo
S
S
Shiraki
K
K
D000818:Animals; D000870:Anterior Horn Cells / Q000201:enzymology*; D000914:Antibodies, Viral / Q000097:blood*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018139:Simplexvirus / Q000235:genetics* / Q000276:immunology; D017735:Virus Latency; D001616:beta-Galactosidase / Q000235:genetics*
D000914:Antibodies, Viral; D001616:beta-Galactosidase