Intrathecal injection of a therapeutic gene-containing polyplex to treat spinal cord injury

J Control Release. 2015 Jan 10;197:1-9. doi: 10.1016/j.jconrel.2014.10.027. Epub 2014 Nov 4.


Spinal cord injury (SCI) is a serious clinical problem that suddenly deprives patients of neurologic function and drastically diminishes their quality of life. Gene introduction has the potential to be effective for various pathological states of SCI because various proteins can be produced just by modifying nucleic acid sequences. In addition, the sustainable protein expression allows to maintain its concentration at an effective level at the target site in the spinal cord. Here we propose an approach using a polyplex system composed of plasmid DNA (pDNA) and a cationic polymer, poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)], that has high capacity to promote endosome escape and the long-term safety by self-catalytically degrading within a few days. We applied brain-derived neurotrophic factor (BDNF)-expressing pDNA for SCI treatment by intrathecal injection of PAsp(DET)/pDNA polyplex. A single administration of polyplex for experimental SCI provided sufficient therapeutic effects including prevention of neural cell death and enhancement of motor function recovery. This lasted for a few weeks after SCI, demonstrating the capability of this system to express BDNF in a safe and responsible manner for treatment of various pathological states in SCI.

Keywords: Brain-derived neurotrophic factor (BDNF); Gene delivery; Intrathecal injection; Polyplex; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Behavior, Animal
  • Brain-Derived Neurotrophic Factor / genetics*
  • Cytokines / genetics
  • DNA / administration & dosage*
  • Female
  • Gene Transfer Techniques
  • Injections, Spinal
  • Mice, Inbred C57BL
  • Peptides / administration & dosage*
  • Plasmids
  • Polymers / administration & dosage*
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy*


  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • PAsp(DET)
  • Peptides
  • Polymers
  • DNA