title: Intrathecal injection of helper-dependent adenoviral vectors results in long-term transgene expression in neuroependymal cells and neurons.
abstract: Helper-dependent adenoviral (HDAd) vectors are devoid of all viral genes and result in long-term transgene expression in the absence of chronic toxicity. Because of their ability to infect post-mitotic cells, including cells of the central nervous system, HDAd vectors are particularly attractive for brain-directed gene therapy. In this study, we show that intrathecal injection of HDAd results in extensive transduction of ependymal cells and sustained expression of the transgene up to 1 year post-administration. We also demonstrate, for the first time, the ability of HDAd injected by this route of delivery to transduce neuronal cells. The transduced neuroepithelial cells can be potentially used to secrete therapeutic proteins into the cerebrospinal fluid and provide them via cross-correction to nontransduced cells. Targeting of neuronal cells and long-term transgene expression make this approach attractive for the treatment of several neurologic diseases.
authors.affiliation: College of Veterinary Medicine and Biomedical Sciences, Veterinary Pathobiology, Texas A&M University, College Station, TX 77843-4467, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Dindot
authors.forename: Pasquale
authors.initials: P
authors.lastname: Piccolo
authors.forename: Nathan
authors.initials: N
authors.lastname: Grove
authors.forename: Donna
authors.initials: D
authors.lastname: Palmer
authors.forename: Nicola
authors.initials: N
authors.lastname: Brunetti-Pierri
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004805:Ependyma / Q000378:metabolism*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006378:Helper Viruses / Q000235:genetics; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046569:Neuroepithelial Cells; D009474:Neurons / Q000378:metabolism*; D014161:Transduction, Genetic / Q000379:methods*; D019076:Transgenes / Q000235:genetics*