title: Lentiviral vectors express chondroitinase ABC in cortical projections and promote sprouting of injured corticospinal axons.
abstract: 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.
authors.affiliation: Cambridge Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK. rz239@cam.ac.uk
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Zhao
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Muir
authors.forename: João Nuno
authors.initials: JN
authors.lastname: Alves
authors.forename: Hannah
authors.initials: H
authors.lastname: Rickman
authors.forename: Anna Y
authors.initials: AY
authors.lastname: Allan
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Kwok
authors.forename: Kasper C D
authors.initials: KC
authors.lastname: Roet
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Schneider
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Bensadoun
authors.forename: Sherif G
authors.initials: SG
authors.lastname: Ahmed
authors.forename: Rafael J
authors.initials: RJ
authors.lastname: Yáñez-Muñoz
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Keynes
authors.forename: James W
authors.initials: JW
authors.lastname: Fawcett
authors.forename: John H
authors.initials: JH
authors.lastname: Rogers
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology*; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D005822:Genetic Vectors / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D051379:Mice; D009416:Nerve Regeneration / Q000235:genetics*; D011712:Pyramidal Tracts / Q000201:enzymology; D051381:Rats; D012756:Sheep; D013119:Spinal Cord Injuries / Q000201:enzymology* / Q000235:genetics
chemical_list: D019765:Chondroitin ABC Lyase