A novel gene delivery system targeting urokinase receptor

Xing Hui Sun, Li Tan, Chun Yang Li, Chang Tong, Jin Fan, Ping Li, Yun Song Zhu

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Recombinant proteins that combine different functions required for cell targeting and intracellular delivery of DNA present an attractive approach for the development of nonviral gene delivery vectors. Here, we described a novel protein termed ATF-lys10 which facilitated cell-specific gene transfer via receptor-mediated endocytosis. ATF-lys10 was composed of the amino-terminal fragment of urokinase and ten lysines at the carboxyl terminus. Bacterially expressed ATF-lys10 protein existed in soluble form, and had antigenicity of human urokinase. Purified ATF-lys10 specifically bound to uPAR-expressing cells and formed protein-DNA complexes with plasmid pGL3-control. After neutralization of excess negative charge with poly-L-lysine, these complexes served as a specific gene delivery vector for uPAR-expressing cells. Lysosomotropic compounds, such as chloroquine, drastically increased the ATF-lys10 mediated gene delivery efficiency. Our results suggest that the recombinant protein ATF-lys10 with the properties of DNA binding and tumor cell targeting represents a promising method for gene transfer and expression in tumor cells.

Original languageEnglish (US)
Pages (from-to)485-491
Number of pages7
JournalActa Biochimica et Biophysica Sinica
Volume36
Issue number7
DOIs
StatePublished - Jul 2004

Keywords

  • Amino-terminal fragment
  • Endocytosis
  • Gene transfer
  • Urokinase
  • Urokinase receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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