Lentiviral vectors express chondroitinase ABC in cortical projections and promote sprouting of injured corticospinal axons.

Autor: Zhao RR; Cambridge Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK. rz239@cam.ac.uk, Muir EM, Alves JN, Rickman H, Allan AY, Kwok JC, Roet KC, Verhaagen J, Schneider BL, Bensadoun JC, Ahmed SG, Yáñez-Muñoz RJ, Keynes RJ, Fawcett JW, Rogers JH
Jazyk: angličtina
Zdroj: Journal of neuroscience methods [J Neurosci Methods] 2011 Sep 30; Vol. 201 (1), pp. 228-38. Date of Electronic Publication: 2011 Aug 09.
DOI: 10.1016/j.jneumeth.2011.08.003
Abstrakt: Several diseases and injuries of the central nervous system could potentially be treated by delivery of an enzyme, which might most effectively be achieved by gene therapy. In particular, the bacterial enzyme chondroitinase ABC is beneficial in animal models of spinal cord injury. We have adapted the chondroitinase gene so that it can direct secretion of active chondroitinase from mammalian cells, and inserted it into lentiviral vectors. When injected into adult rat brain, these vectors lead to extensive secretion of chondroitinase, both locally and from long-distance axon projections, with activity persisting for more than 4 weeks. In animals which received a simultaneous lesion of the corticospinal tract, the vector reduced axonal die-back and promoted sprouting and short-range regeneration of corticospinal axons. The same beneficial effects on damaged corticospinal axons were observed in animals which received the chondroitinase lentiviral vector directly into the vicinity of a spinal cord lesion.
(Copyright © 2011 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: