Hypoxia-inducible gene expression system using the erythropoietin enhancer and 3′-untranslated region for the VEGF gene therapy

Minhyung Lee, Donghoon Choi, Min Ji Choi, Ji Hoon Jeong, Won Jong Kim, Seungjoon Oh, Yong Hee Kim, David A. Bull, Sung Wan Kim

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Gene therapy with the vascular endothelial growth factor (VEGF) gene is a potential treatment for many disorders or injuries with ischemia. However, unregulated expression of VEGF may induce pathological angiogenesis, promoting tumor growth, diabetic proliferative retinopathy and rupture of atherosclerotic plaque. Therefore, the effective regulation of the gene expression is one of the requirements for the VEGF gene therapy. In this research, we evaluated the hypoxia-inducible gene expression system with the erythropoietin (Epo) enhancer and the Epo 3′-untranslated region (UTR). The luciferase plasmids were constructed with the Epo enhancer (pEpo-SV-Luc), the Epo 3′-UTR (pSV-Luc-EpoUTR) or both (pEpo-SV-Luc-EpoUTR). The polyethylenimine/plasmid complexes were transfected to 293 or A7R5 cells and the cells were incubated under normoxia or hypoxia. The results showed that the Epo enhancer or Epo 3′-UTR increased the target gene expression under hypoxia. pEpo-SV-Luc-EpoUTR showed the highest luciferase expression. The VEGF expression plasmid with the Epo enhancer and 3′-UTR was also constructed. The VEGF expression by pEpo-SV-VEGF-EpoUTR showed the highest specificity of the gene expression in the hypoxic cells. The results suggest that the VEGF plasmid with the Epo enhancer and the Epo 3′-UTR may be useful for gene therapy for ischemic diseases.

Original languageEnglish
Pages (from-to)113-119
Number of pages7
JournalJournal of Controlled Release
Issue number1
Publication statusPublished - 2006 Sept 28

Bibliographical note

Funding Information:
This research was financially supported by National Institutes of Health grant HL65477, HL071541 and the Ministry of Science and Technology (M1041403002-05N1403-00212 and M10534030003-05N3403-00310) in Korea.

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


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