Terashima, T., Oka, K., Kritz, A. B., Kojima, H., Baker, A. H. and Chan, L. (2009) DRG-targeted helper-dependent adenoviruses mediate selective gene delivery for therapeutic rescue of sensory neuronopathies in mice. Journal of Clinical Investigation, 119(7), pp. 2100-2112. (doi: 10.1172/JCI39038)
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Publisher's URL: http://dx.doi.org/10.1172/JCI39038
Abstract
Dorsal root ganglion (DRG) neuron dysfunction occurs in a variety of sensory neuronopathies for which there are currently no satisfactory treatments. Here we describe the development of a strategy to target therapeutic genes to DRG neurons for the treatment of these disorders. We genetically modified an adenovirus (Ad) to generate a helper virus (HV) that was detargeted for native adenoviral tropism and contained DRG homing peptides in the adenoviral capsid fiber protein; we used this HV to generate DRG-targeted helper-dependent Ad (HDAd). In mice, intrathecal injection of this HDAd produced a 100-fold higher transduction of DRG neurons and a markedly attenuated inflammatory response compared with unmodified HDAd. We also injected HDAd encoding the β subunit of β-hexosaminidase (Hexb) into Hexb-deficient mice, a model of the neuronopathy Sandhoff disease. Delivery of the DRG-targeted HDAd reinstated neuron-specific Hexb production, reversed gangliosidosis, and ameliorated peripheral sensory dysfunction. The development of DRG neuron–targeted HDAd with proven efficacy in a preclinical model may have implications for the treatment of sensory neuronopathies of diverse etiologies.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Baker, Professor Andrew |
| Authors: | Terashima, T., Oka, K., Kritz, A. B., Kojima, H., Baker, A. H., and Chan, L. |
| Subjects: | Q Science > QH Natural history > QH345 Biochemistry |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Journal of Clinical Investigation |
| Publisher: | Americal Society for Clinical Investigation |
| ISSN: | 0021-9738 |
| ISSN (Online): | 1558-8238 |
| Published Online: | 15 June 2009 |
| Copyright Holders: | Copyright © 2009 American Society for Clinical Investigation |
| First Published: | First published in Journal Of Clinical Investigation 119(7):2100-2112 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
| Related URLs: |
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