期刊
MOLECULAR THERAPY
卷 13, 期 5, 页码 870-881出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2005.12.013
关键词
HSV; ICP10PK; neuroprotection; gene therapy; kainic acid; seizures; glia
资金
- NIEHS NIH HHS [T32 ES007263, ES07263] Funding Source: Medline
- NINDS NIH HHS [NS40338, R01 NS040338, NS45169, R01 NS045169] Funding Source: Medline
Identification of targets and delivery platforms for gene therapy of neurodegenerative disorders is a clinical challenge. We describe a novel paradigm in which the neuroprotective gene is the herpes simplex virus type 2 (HSV-2) antiapoptotic gene ICP10PK and the vector is the growth-com promised HSV-2 mutant ARR. ARR is delivered intranasally. It is not toxic in rats and mice. ICP10PK is expressed in the hippocampus of the ARR-treated animals for at least 42 days in the absence of virus replication and late virus gene expression. Its expression is regulated by an AP-1 amplification loop. Intranasally delivered ARR prevents kainic acid-induced seizures, neuronal loss, and inflammation, in both rats and mice. The data suggest that ARR is a promising therapeutic platform for neurodegenerative diseases.
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