Transferrin-polycation/DNA

Wightman, L., Patzelt, E., Wagner, E. and Kircheis, R. (1999) Development of transferrin-polycation/DNA based vectors for gene delivery to melanoma cells. J. Drug Target., 7, 293-303. 

Wagner E, Cotton M, Foisner R, et al. Transferrin-polycation-DNA complexes the effect of polycations on the structure of the complex DMA delivery to cells. Proc Natl Acad Sci U S A1991 88 4255-4259. 

Cotten M, Langle-Rouault F, Kirlappos H, Wagner E, Mechtler K, Zenke M, Beug H, Bimstiel ML (1990) Transferrin-polycation-mediated introduction of DNA into human leukemic cells stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels. Proc Natl Acad Sci USA 87 4033 4037... 

Zenke, M., Steinlein, P., Wagner, E., Cotten, M.,Beug, H. and Bimstiel, M.L. (1990) Receptor-mediated endocytosis of transferrin-polycation conjugates an efficient way to introduce DNA into hematopoietic cells. Proc. Natl. Acad. 

Wagner E, Zenke M, Cotten M, Beug H, Brinstiel ML. Transferrin-polycation conjugates as carriers for DNA uptake into cells. Proc Natl Acad Sci USA 1990, 87, 3410-3414. 

Early experiments showed that a transferrin-polycation complex transported bacterial DNA into cells [12]. Ions are taken up by cells as an iron-transferrin complex by receptor-mediated endocytosis. Protamine or poly-lysine ligated by disulfide bonds to transferring and mixed with a lu-ciferase-encoding plasmid may bind the DNA because of the cationic properties of the complex [12]. Subsequently, avian ery-throblasts and human K-562 cells were incubated with the transferrin-polycation peptide-DNA complex, and the complexes were recognized and transported into the cells by receptor-mediated endocytosis and taken up into endosome-Hke intracellular vesicles [12]. Treatment with chloroquine (an agent that affects the endosomal pH) enhanced the uptake considerably. In contrast to other transfection methods, the transfection of cells with transferrin-mediated endocytosis did not cause significant cell death, because of the physiologi-... 

The transferrin receptor was one of the first to be exploited for receptor-mediated gene delivery. All actively metabolising cells require iron that is internalised by the cell as a transferrin-iron complex by means of receptor mediated endocytosis. To exploit this ubiquitous and efficient transport mechanism for introducing DNA into cells, conjugates of chicken or human transferrin with polycations (polylysine or protamine) were synthesised and used to form complexes with plasmid DNA. The number of transferrin molecules attached to each polylysine molecule varies according to the molecular weight of the polymer, but is generally around 1 transferrin molecule for every 50 lysine residues. ... 

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