Neurotoxic reactions of CNS cells following gene transfer with defective herpes simplex virus (HSV-1) vector

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Abstract
Defective herpes simplex virus (HSV-1) vector containing either the lac-z gene or the tyrosine-hydroxylase (TH) gene was added to primary rat neocortex cultures and gene transfer was assessed using immunohistochemical procedures. While we were able to confirm lac- and TH-expression in vitro, exposure to the vector was accompanied by marked neurotoxic reactions as indicated by severe cell loss in vitro. Furthermore, when genetically altered cells were implanted into the adult rat striatum, a few lac-z positive cells without neurites were present but not a single TH-expressing cell could be found. The value of the HSV-1 vector system to transfer genes in the adult rat brain should therefore be viewed with caution.

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