title: Absence of an intrathecal immune reaction to a helper-dependent adenoviral vector delivered into the cerebrospinal fluid of non-human primates.
abstract: 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.
authors.affiliation: Neuroimmunology Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Butti
authors.forename: A
authors.initials: A
authors.lastname: Bergami
authors.forename: A
authors.initials: A
authors.lastname: Recchia
authors.forename: E
authors.initials: E
authors.lastname: Brambilla
authors.forename: D
authors.initials: D
authors.lastname: Franciotta
authors.forename: A
authors.initials: A
authors.lastname: Cattalini
authors.forename: A
authors.initials: A
authors.lastname: Stornaiuolo
authors.forename: F
authors.initials: F
authors.lastname: Lachapelle
authors.forename: G
authors.initials: G
authors.lastname: Comi
authors.forename: F
authors.initials: F
authors.lastname: Mavilio
authors.forename: G
authors.initials: G
authors.lastname: Martino
authors.forename: R
authors.initials: R
authors.lastname: Furlan
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002555:Cerebrospinal Fluid / Q000821:virology*; D015870:Gene Expression; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000276:immunology; D006378:Helper Viruses / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D008252:Macaca fascicularis; D008297:Male; D023421:Models, Animal; D046569:Neuroepithelial Cells / Q000276:immunology / Q000821:virology; D010300:Parkinson Disease / Q000276:immunology / Q000628:therapy*; D013129:Spinal Puncture; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D015847:Interleukin-4