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- Title
Adeno-associated virus vector-mediated bcl-2 gene transfer into post-ischemic gerbil brain in vivo: prospects for gene therapy of ischemia-induced neuronal death.
- Authors
Shimazaki, K; Urabe, M; Monahan, J; Ozawa, K; Kawai, N
- Abstract
The proto-oncogene bcl-2 is known as an anti-apoptotic gene that confers the ability to block neuronal ceil death after transient ischemia. In order to examine whether the bcl-2 gene can be used for protection of ischemic brain injury, we generated adeno-associated virus (AAV) vectors capable of expressing human bcl-2. Replication-defective AAV vectors were found effectively to transfer and express bcl-2 gene in the gerbil hippocampal neurons. Transduction with AAV bcl-2 5 days before forebrain ischemia prevented the DNA fragmentation in the CA1 neurons that is commonly associated with ischemia-induced ceil death. Furthermore, the application of AAV bcl-2 as late as 1 h following an ischemic insult also prevented DNA fragmentation in CA1 neurons. These results suggest that the bcl-2 protein has neuroprotective functions that inhibit ischemic cell death and demonstrate the potential of AAV bcl-2 for use in post-ischemic gene therapy in the brain.
- Subjects
ADENOVIRUSES; BRAIN; GERBILS; GENE therapy
- Publication
Gene Therapy, 2000, Vol 7, Issue 14, p1244
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301211