Gene transfer to dorsal root ganglia by intrathecal injection: effects on regeneration of peripheral nerves

Mol Ther. 2005 Aug;12(2):314-20. doi: 10.1016/j.ymthe.2005.03.032.

Abstract

Gene delivery to sensory neurons of the dorsal root ganglion (DRG) offers the prospect of developing new clinical interventions against peripheral nerve diseases and disorders. Here we show that genes can be transferred to rat DRG through lumbar intrathecal injection of delivery vectors into the cerebrospinal fluid. Genes could be transferred to DRG using polyethylenimine (PEI)/DNA complexes, Lipofectamine 2000/DNA complexes, adeno-associated virus vectors, or baculovirus vectors. We also show that nerve growth factor cDNA, delivered through lumbar intrathecal injection of PEI complexes, was able to improve regeneration of transected rat sciatic nerves. These data demonstrate the viability of using an intrathecal gene delivery approach for treating peripheral neuropathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviridae / genetics
  • DNA, Complementary / metabolism*
  • Dependovirus / genetics
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / physiology*
  • Gene Expression
  • Gene Transfer Techniques*
  • Genes, Reporter
  • Genetic Vectors
  • Injections, Spinal
  • Lipids / genetics
  • Liposomes
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • Nerve Growth Factors
  • Nerve Regeneration* / genetics
  • Polyethyleneimine
  • Rats
  • Rats, Wistar
  • Sciatic Nerve / physiology*

Substances

  • DNA, Complementary
  • Lipids
  • Lipofectamine
  • Liposomes
  • Nerve Growth Factors
  • Polyethyleneimine
  • Luciferases