Therapeutic effects of a reducible poly (oligo-d-arginine) carrier with the heme oxygenase-1 gene in the treatment of hypoxic-ischemic brain injury

Hyesun Hyun, Young Wook Won, Kyung Min Kim, Jiyoung Lee, Minhyung Lee, Yong-Hee Kim

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Non-viral carriers for gene therapy have been developed to minimize carrier cytotoxicity and to enhance transfection efficiency. Previously, we synthesized a 9-arginine-based reducible high molecular weight peptide for gene delivery. For the reducible poly(oligo- d-arginines) (rPOA), 9-arginine oligopeptides are connected by internal disulfide linkages to produce a high molecular weight peptide. In this study, rPOA was evaluated as a carrier of the heme oxygenase-1 (HO-1) gene for the treatment of ischemia/reperfusion (I/R) -induced brain stroke. An in vitro transfection assay showed that rPOA had higher transfection efficiency and lower toxicity than polyethylenimine (PEI). For in vivo evaluation, I/R rat models were produced by middle cerebral artery occlusion (MCAO). rPOA/HO-1 expression plasmid (pHO-1) polyplexes were injected into the brain at 1 h before MCAO, and HO-1 expression levels in the brain were then measured by ELISA. The results indicated that rPOA/pHO-1 polyplexes had higher transfection efficiencies than PEI/pHO-1 polyplexes. The rPOA/pHO-1 polyplexes significantly reduced infarct volumes. In addition, tumor necrosis factor-alpha (TNF-α) was reduced in the rPOA/pHO-1 polyplex injection group, suggesting that HO-1 had an anti-inflammatory effect, while the PEI/pHO-1 polyplex did not show this effect. These results suggest that rPOA is a potential non-viral vector for HO-1 gene therapy to protect brain cells from I/R-related neuronal injury including stroke.

Original languageEnglish
Pages (from-to)9128-9134
Number of pages7
JournalBiomaterials
Volume31
Issue number34
DOIs
StatePublished - 2010 Dec 1

Keywords

  • Animal model
  • Gene expression
  • Gene therapy
  • In vivo test
  • Peptide

Fingerprint Dive into the research topics of 'Therapeutic effects of a reducible poly (oligo-d-arginine) carrier with the heme oxygenase-1 gene in the treatment of hypoxic-ischemic brain injury'. Together they form a unique fingerprint.

  • Cite this