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Efficient GLP-1 gene delivery using two-step transcription amplification plasmid system with a secretion signal peptide and arginine-grafted bioreducible polymer

Title
Efficient GLP-1 gene delivery using two-step transcription amplification plasmid system with a secretion signal peptide and arginine-grafted bioreducible polymer
Author
이민형
Keywords
Gene delivery; Glucagon-like peptide-1; Two-step transcription amplification; Secretion signal peptide; Arginine-grafted bioreducible polymer
Issue Date
2012-01
Publisher
Elsevier Science B.V., Amsterdam.
Citation
Journal of Controlled Release, Vol.157, No.2 [2012], p243-248
Abstract
Glucagon-like peptide (GLP-1) encoding dual plasmid (pDNA) system (TSTA (SP-GLP-1)) which is composed of pβ-Gal4-p65 and pUAS-SP-GLP-1 was constructed to improve the production and secretion of expressed GLP-1 by combining the advantages of signal peptide (SP) and two-step transcription amplification (TSTA) system. Its potential for GLP-1 gene delivery system was investigated with employment of arginine-grafted bioreducible polymer (ABP) as a gene carrier. Their polyplexes have about 140nm-sizes and 20mV Zeta-potential values. ABP showed no cytotoxicity contrary to PEI25k. It was found in RT-PCR experiments that TSTA-SP pDNA systems showed increased GLP-1 gene transcription level in comparison with mono pDNA system (pβ-GLP-1). It was also observed in GLP-1 ELISA that GLP-1 secretion level of TSTA (SP-GLP-1) pDNA system was 2.7–3.4 times higher than those of pβ-GLP-1 and 1.5–1.7 times than TSTA (GLP-1). Additionally, 2.5–3.5 folds increased level of GLP-1 secretion was found in ABP gene carrier system in comparison with PEI25k. When transfection medium containing secreted GLP-1 was transferred to NIT-1 insulinoma cells, the highest secretion level of insulin was induced in ABP/TSTA (SP-GLP-1) polyplex medium-treated cells. Therefore, this novel system could be utilized as a safe and efficient GLP-1 gene delivery system for type 2 diabetes therapy.
URI
http://www.sciencedirect.com/science/article/pii/S0168365911008571?via%3Dihubhttp://hdl.handle.net/20.500.11754/67191
ISSN
0168-3659
DOI
10.1016/j.jconrel.2011.09.072
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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