Non-viral polymeric gene carriers have been widely investigated but no promising biocompatible
polymer was developed for the gene therapy of neural system
injuries yet. This study evaluated the potential usage of
water-soluble lipopolymer (WSLP) as a gene delivery vehicle in neural lineage cells of SK-N-BE(2)C, a
neuroblastoma cell line and primary culture of mouse neural progenitor cells (mNPCs). When tested with the
luciferase reporter (pSV-Luc), WSLP showed higher gene transfection efficiency by more than 8-10 folds yet with lower cytotoxicity than
polyethylenimine of 1800 Da (PEI1800), a parental
polymer, and
Lipofectamine 2000. The optimum N/P ratios were 40:1 for WSLP and 10:1 for PEI1800, respectively. The transfection efficiency for both of WSLP and PEI1800 was higher overall in SK-N-BE(2)C cells than in mNPCs. WSLP was also used successfully for the delivery and
hypoxia-inducible expression of
luciferase reporter plasmid containing the
erythropoietin (Epo) enhancer (pEpo-SV-Luc) or RTP801 promoter (pRTP801-Luc). The
hypoxia-inducible system and WSLP were then successfully applied to the delivery of
granulocyte macrophage colony-stimulating factor (
GM-CSF) gene that was previously shown to have
neuroprotective effect on neural cell death in vitro and in rat SCI model. The
hypoxia-inducible
GM-CSF plasmids (pEpo-SV-GM-CSF and pRTP801-GM-CSF) showed induced expression of
GM-CSF under
hypoxia and decrease in the
hypoxia-induced cell death in SK-N-BE(2)C cells. In conclusion, this study demonstrated that WSLP could be an efficient gene delivery carrier for neural cells and gene therapy of
GM-CSF using the
hypoxia-inducible system could be a potential therapeutic intervention for neural
injuries. Further studies are necessary to confirm the current findings in animal models of CNS
injuries.