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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
Source :
Journal of Controlled Release. Oct2006, Vol. 115 Issue 3, p316-321. 6p.
Publication Year :
2006

Abstract

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 pβ-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, pβ-Gal4-p65 and pUAS-Luc were constructed. The pUAS-Luc/pβ-Gal4-p65 system showed the highest transfection efficiency at a 2:1 pUAS-Luc/pβ-Gal4-p65 weight ratio. In addition, the transgene expression by the TSTA system was at least 4 times higher than pβ-Luc. To apply the TSTA system to the GLP-1 expression plasmid, pUAS-GLP-1 was constructed. The pUAS-GLP-1/pβ-Gal4-p65 system showed higher mRNA level than pβ-GLP-1. In addition, the level of GLP-1 by the pUAS-GLP-1/pβ-Gal4-p65 system was more than 4 times higher than pβ-GLP-1. Therefore, the TSTA GLP-1 expression system may be useful to develop gene therapy system for type 2 diabetes. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
01683659
Volume :
115
Issue :
3
Database :
Academic Search Index
Journal :
Journal of Controlled Release
Publication Type :
Academic Journal
Accession number :
22936188
Full Text :
https://doi.org/10.1016/j.jconrel.2006.07.017