An efficient GLP-1 expression system using two-step transcription amplification
- Authors
- Lee, Minhyung; Oh, Seungjoon; Ahn, Cheol-Hee; Kim, Sung Wan; Rhee, Byoung Doo; Ko, Kyung Soo
- Issue Date
- Oct-2006
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- diabetes; gene therapy; glucagon-like peptide 1; two-step transcription amplification
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.115, no.3, pp.316 - 321
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 115
- Number
- 3
- Start Page
- 316
- End Page
- 321
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/180917
- DOI
- 10.1016/j.jconrel.2006.07.017
- ISSN
- 0168-3659
- Abstract
- Glucagon-like peptide 1 (GLP-1) is an insulinotropic protein. It was reported that the continuous infusion of GLP-1 normalized the blood glucose level in type 2 diabetes animal model. However, the short half-life of GLP-1 has limited its application in clinical settings and prompted us to develop a GLP-1 gene therapy system. Our previous results showed that the delivery of p beta-GLP-1 using polyethylenimine (PEI) reduced the blood glucose level effectively. However, the glucose level was not completely normalized. In the present study, the more efficient GLP-1 expression system was developed using two-step transcription amplification (TSTA). To evaluate the TSTA system, p beta-Ga14-p65 and pUAS-Luc were constructed. The pUAS-Luc/p13-Ga14-p65 system showed the highest transfection efficiency at a 2:1 pUAS-Luc/p beta-Ga14-p65 weight ratio. In addition, the transgene expression by the TSTA system was at least 4 times higher than p beta-Luc. To apply the TSTA system to the GLP-1 expression plasmid, pUAS-GLP-1 was constructed. The pUAS-GLP-1/p beta-Ga14-p65 system showed higher mRNA level than p beta-GLP-1. In addition, the level of GLP-1 by the pUAS-GLP-1/p13-Ga14-p65 system was more than 4 times higher than p beta-GLP-1. Therefore, the TSTA GLP-1 expression system may be useful to develop gene therapy system for type 2 diabetes.
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