Absence of an intrathecal immune reaction to a helper-dependent adenoviral vector delivered into the cerebrospinal fluid of non-human primates

Butti, E.; Bergami, A.; Recchia, A.; Brambilla, E.; Franciotta, D.; Cattalini, A.; Stornaiuolo, A.; Lachapelle, F.; Comi, G.; Mavilio, F.; Martino, G.; Furlan, R.
February 2008
Gene Therapy;Feb2008, Vol. 15 Issue 3, p233
Academic Journal
Inflammation and immune reaction, or pre-existing immunity towards commonly used viral vectors for gene therapy severely impair long-term gene expression in the central nervous system (CNS), impeding the possibility to repeat the therapeutic intervention. Here, we show that injection of a helper-dependent adenoviral (HD-Ad) vector by lumbar puncture into the cerebrospinal fluid (CSF) of non-human primates allows long-term (three months) infection of neuroepithelial cells, also in monkeys bearing a pre-existing anti-adenoviral immunity. Intrathecal injection of the HD-Ad vector was not associated with any sign of systemic or local toxicity, nor by signs of a CNS-specific immune reaction towards the HD-Ad vector. Injection of HD-Ad vectors into the CSF circulation may thus represent a valuable approach for CNS gene therapy allowing for long-term expression and re-administration.Gene Therapy (2008) 15, 233–238; doi:10.1038/sj.gt.3303050; published online 25 October 2007


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