Augmentation of erythropoietin enhancer-mediated hypoxia-inducible gene expression by co-transfection of a plasmid encoding hypoxia-inducible factor 1 for ischemic tissue targeting gene therapy
- Authors
- Lee, Suyeon; Kim, Kyunghwa; Kim, Hyun Ah; Kim, Sung Wan; Lee, Minhyung
- Issue Date
- Jan-2008
- Publisher
- TAYLOR & FRANCIS LTD
- Keywords
- angiogenic growth factor; erythropoietin enhancer; hypoxia-inducible factor 1 alpha; ischemia; transcription regulation
- Citation
- JOURNAL OF DRUG TARGETING, v.16, no.1, pp.43 - 50
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF DRUG TARGETING
- Volume
- 16
- Number
- 1
- Start Page
- 43
- End Page
- 50
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/179099
- DOI
- 10.1080/10611860701699693
- ISSN
- 1061-186X
- Abstract
- Therapeutic angiogenesis with gene encoding vascular endothelial growth factor (VEGF) is a potential treatment for ischemic diseases. However, VEGF expression should be tightly regulated to avoid side effects such as tumor growth. Previously, our group developed the erythropoietin (Epo) enhancer-SV40 promoter system for hypoxia-specific gene expression. In the present study, the activity of the Epo enhancer-SV40 promoter system was further enhanced without significant decrease in its specificity by co-transfection of the hypoxia-inducible factor 1 alpha (HIF1 alpha) gene. pSV-HIF1 alpha was constructed by the insertion of the HIF1 alpha cDNA into pSI. At a 1:1 ratio, co-transfection of pSV-HIF1 alpha and pEpo-SV-Luc increased the promoter activity of the Epo enhancer-SV40 promoter system, showing at least three times higher gene expression under hypoxia as compared with the pEpo-SV-Luc single-plasmid transfection. Furthermore, co-transfection showed significant hypoxia specificity. Also, co-transfection of pEpo-SV-VEGF with pSV-HIF1 alpha showed the enhanced VEGF expression without loss of hypoxia specificity, as compared with pEpo-SV-VEGF single-plasmid transfection. Furthermore, pSV-HIF1 alpha induced the endogenous hypoxia-responsive genes such as angiopoietin-1, which would be beneficial for therapeutic angiogenesis. Therefore, with hypoxia specificity and higher gene expression, co-transfection of pSV-HIF1 alpha and pEpo-SV-VEGF may be useful for ischemia targeting gene therapy.
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