A rapid and convenient method to enhance transgenic expression in target cells

Chia Hung Chen, Yen Ku Liu, Yu Ling Lin, Huai Yao Chuang, Wei Tung Hsu, Yi Han Chiu, Tian Lu Cheng, Kuang-Wen Liao*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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)-B, 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 v3 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.

Original languageEnglish
Pages (from-to)448-461
Number of pages14
JournalPreparative Biochemistry and Biotechnology
Volume42
Issue number5
DOIs
StatePublished - 1 Sep 2012

Keywords

  • integrin v3
  • polyethyleneimine (PEI)
  • RGD-4C-HA
  • transcription factor-based synthetic promoter (TSP)

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