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A novel gene delivery system targeting urokinase receptor.

Authors
Type
Published Article
Journal
Acta biochimica et biophysica Sinica
Publication Date
Volume
36
Issue
7
Pages
485–491
Identifiers
PMID: 15248023
Source
Medline
License
Unknown

Abstract

Recombinant proteins that combine different functions required for cell targeting and intra-cellular 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. Lyso-somotropic 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.

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