A simple and efficient method of protein delivery into cells using adenovirus.
Human adenovirus type 2 has been previously shown to increase the delivery of a variety of proteins into cells when Ad is co-internalized with the protein ligands. To increase the efficiency of adenoviral-mediated delivery of proteins, I have linked adenovirus, separately with two proteins, epidermal growth factor and an antibody against human transferrin receptor through disulfide and thioether linkages. Competition experiments indicate that the conjugates are taken up into the cells through adenovirus receptor. During the internalization of adenovirus-protein conjugates into KB cells, the conjugates were equally effective as the native adenovirus in disrupting endocytic vesicles and releasing their protein content into the cytosol. This implies the possible use of adenovirus to deliver a large number of protein molecules into the cells.
Seth
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Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
D000260:Adenoviruses, Human / Q000502:physiology*; D000906:Antibodies / Q000378:metabolism* / Q000633:toxicity; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007457:Iodine Radioisotopes; D007624:KB Cells; D007700:Kinetics; D014176:Protein Biosynthesis / Q000187:drug effects; D011990:Receptors, Transferrin / Q000276:immunology*; D011991:Receptors, Virus / Q000502:physiology*; D013462:Sulfur Radioisotopes
D000906:Antibodies; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D011990:Receptors, Transferrin; D011991:Receptors, Virus; D013462:Sulfur Radioisotopes; D004815:Epidermal Growth Factor