| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
In order to evaluate the adaptability of an attenuated herpes simplex virus vector(βH1) expressing β-galactosidase, as a foreign gene, to gene therapy of nerve-muscle diseases, βH1 gene expression in spinal cord(SC) and gastrocnemius muscle compared with the dorsal root ganglia(DRG) were characterized. We found that βH1 driven by UL 55 gene promoter expressed β-galactosidase and glycoprotein C, which are late viral proteins, and their mRNAs in neurons of the bilateral anterior gray horns of SC of rats in acute and latent stage after intramuscular and intradermal infections but not in the DRG in the latent stage. β-Galactosidase activity was also detected in gastrocnemius muscle at 7 days to 10 months but not its mRNA in at the 10 months. Despite of those gene expressions of βH1 in the SC, no infectious virus was detected. Neither significant pathological changes in the SC and gastrocnemius muscle nor electro-physiological alterations on sciatic nerve-gastrocnemius muscle function were observed. Therefore, mode of the latent gene expression of βH1 in the SC of rats, which might contribute to its attenuation, was indicated to be novel and different from that in the DRG. These results suggested the potential use of replication-competent βH1 for gene therapy into nerve-muscle disease. Now a new βH1 expressing BDNF(brain derived nerve growth factor) has been trying to be developed. In near future, using this new HSV vector, the functional changes in nerve-muscle disease would be analyzed.
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