Transferrin-polycation conjugates as carriers for DNA uptake into cells.
We have developed a high-efficiency nucleic acid delivery system that uses receptor-mediated endocytosis to carry DNA macromolecules into cells. We accomplished this by conjugating the iron-transport protein transferrin to polycations that bind nucleic acids. Human transferrin, as well as the chicken homologue conalbumin, has been covalently linked to the small DNA-binding protein protamine or to polylysines of various sizes through a disulfide linkage. These modified transferrin molecules maintain their ability to bind their cognate receptor and to mediate efficient iron transport into the cell. The transferrin-polycation molecules form electrophoretically stable complexes with double-stranded DNA, single-stranded DNA, and modified RNA molecules independent of nucleic acid size (from short oligonucleotides to DNA of 21 kilobase pairs). When complexes of transferrin-polycation and a bacterial plasmid DNA containing the gene for Photinus pyralis luciferase are supplied to eukaryotic cells, high-level expression of the luciferase gene occurs, demonstrating transferrin receptor-mediated endocytosis and expression of the imported DNA. We refer to this delivery system as "transferrinfection."
Wagner
E
E
Research Institute of Molecular Pathology, Vienna, Austria.
Zenke
M
M
Cotten
M
M
Beug
H
H
Birnstiel
M L
ML
D000818:Animals; D001692:Biological Transport; D002454:Cell Differentiation; D002478:Cells, Cultured; D002645:Chickens; D003207:Conalbumin / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D066246:ErbB Receptors / Q000378:metabolism; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011107:Polylysine / Q000378:metabolism*; D011479:Protamines / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*
D004268:DNA-Binding Proteins; D011479:Protamines; D014168:Transferrin; D003207:Conalbumin; D011107:Polylysine; D004247:DNA; D008156:Luciferases; D066246:ErbB Receptors