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A Novel Gene Delivery System Targeting Urokinase Receptor

查看全文 作  者:Xing-HuiSUN LiTAN Chun-YangLI ChangTONG JinFAN PingLI Yun-[1]SongZHU 高影响力作者 机构地区:[1]DepartmentofMolecularGenetics,KeyLaboratoryofMolecularMedicineofMinistryEducation,ShanghaiMedicalCollegeofFudanUniversity,Shanghai200032,China高影响力机构 出  处:《Acta Biochimica et Biophysica Sinica》索引2004年第36卷第7期,共7页高影响力期刊 基  金:This work was supported by a grant from the National Natural ScienceFoundation of China (No. 30170398) 摘  要: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. 关 键 词:尿激酶 受体 基因迁移 内吞作用 氨基末段片段
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