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

作者：Butti E; Bergami A; Recchia A; Brambilla E; Franciotta D; Cattalini A; Stornaiuolo A; Lachapelle F; Comi G; Mavilio F; Martino G; Furlan R^*

来源：Gene Therapy, 2008, 15(3): 233-238.

DOI：10.1038/sj.gt.3303050

• helper-dependent adenoviral vectors
• central nervous system
• inflammation
• immunogenicity

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.

• 出版日期2008-2