A rapid and convenient method to enhance transgenic expression in target cells.
Gene therapy provides a novel strategy and a new hope for patients with cancer. Unfortunately, the specifics of the delivery systems or the promoters have not achieved the specified efficacy so far, and the perfection of either system will be extremely difficult. In this study, we introduce a simple concept that a combination of a partially specific delivery system and a partially specific promoter activity may achieve a more specific effect on transgenic expression in target cells. The first section describes tumor-related transcription factors that were assayed in tumors or rapidly proliferating cells to determine their activities. The activities of nuclear factor (NF)-κB, CREB, and HIF-1 were higher, and three copies of each response element were used to construct a transcription factor-based synthetic promoter (TSP). The results showed that the expression of the TSP was active and partially specific to cell types. As described in the second section, the multifunctional peptide RGD-4C-HA was designed to absorb polyethyleneimine (PEI) molecules, and this complex was targeted to integrin αvβ3 on B16F10 cells. The results indicated that RGD-4C-HA could associate with PEI to mediate specific targeting in vitro. Finally, the combination of the PEI-peptide complex and TSP could enhance the specifically transgenic expression in B16F10 cells. This strategy has been proven to work in vitro and might potentially be used for specific gene therapy in vivo.
Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsin-Chu, Taiwan, Republic of China.
Chia-Hung
CH
Chen
Yen-Ku
YK
Liu
Yu-Ling
YL
Lin
Huai-Yao
HY
Chuang
Wei-Tung
WT
Hsu
Yi-Han
YH
Chiu
Tian-Lu
TL
Cheng
Kuang-Wen
KW
Liao
D050882:CREB-Binding Protein / Q000737:chemistry / Q000235:genetics; D045744:Cell Line, Tumor; D015870:Gene Expression; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry / Q000235:genetics; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000235:genetics; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D009369:Neoplasms / Q000473:pathology / Q000628:therapy; D009842:Oligopeptides / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry; D020218:Response Elements; D014162:Transfection
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D039302:Integrin alphaVbeta3; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D011094:Polyethyleneimine; D050882:CREB-Binding Protein; C494363:CREBBP protein, human