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

J Neurosci Methods. 2011 Sep 30;201(1):228-38. doi: 10.1016/j.jneumeth.2011.08.003. Epub 2011 Aug 9.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cerebral Cortex / enzymology*
  • Chondroitin ABC Lyase / administration & dosage
  • Chondroitin ABC Lyase / biosynthesis
  • Chondroitin ABC Lyase / genetics*
  • Gene Expression Regulation, Enzymologic*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / biosynthesis
  • Genetic Vectors / genetics*
  • HEK293 Cells
  • Humans
  • Lentivirus / genetics*
  • Male
  • Mice
  • Nerve Regeneration / genetics*
  • Pyramidal Tracts / enzymology
  • Rats
  • Sheep
  • Spinal Cord Injuries / enzymology*
  • Spinal Cord Injuries / genetics

Substances

  • Chondroitin ABC Lyase