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Published Online: 22 December 2010

Intrathecal Injection of Helper-Dependent Adenoviral Vectors Results in Long-Term Transgene Expression in Neuroependymal Cells and Neurons

Publication: Human Gene Therapy
Volume 22, Issue Number 6

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.

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Published In

cover image Human Gene Therapy
Human Gene Therapy
Volume 22Issue Number 6June 2011
Pages: 745 - 751
PubMed: 21175294

History

Published in print: June 2011
Published ahead of print: 18 March 2011
Published online: 22 December 2010
Accepted: 22 December 2010
Received: 10 December 2010

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Scott Dindot
*
College of Veterinary Medicine and Biomedical Sciences, Veterinary Pathobiology, Texas A&M University, College Station, TX 77843-4467.
Pasquale Piccolo*
Telethon Institute of Genetics and Medicine, 80131 Naples, Italy.
Nathan Grove
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030.
Donna Palmer
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030.
Nicola Brunetti-Pierri
Telethon Institute of Genetics and Medicine, 80131 Naples, Italy.
Department of Pediatrics, Federico II University, 80131 Naples, Italy.

Notes

Address correspondence to:Dr. Nicola Brunetti-PierriTelethon Institute of Genetics and MedicineVia P. Castellino, 11180131 NapoliItaly
E-mail: [email protected]

Author Disclosure Statement

The authors declare no conflict of interest.

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