title: Intracellular delivery of functional proteins via decoration with transporter peptides.
abstract: Despite numerous attractive intracellular targets, protein therapeutics have been principally confined to the extracellular space due to the lack of a straightforward way to deliver functional polypeptides to the cell interior. Peptide sequences facilitating intracellular protein delivery have been identified; however, current strategies to apply them require problematic steps, such as generation of new in-frame fusion proteins, covalent chemical conjugation, and denaturation. We have developed a new approach to protein transfer into cells and tissues that relies on single-step decoration by cysteine-flanked, arginine-rich transporter peptides. This approach facilitated cell and tissue delivery of a variety of functional proteins, including antibodies and enzymes. Decoration with transporter peptides thus provides an attractive general means of intracellular delivery of functional proteins in vitro and in tissue.
authors.affiliation: VA Palo Alto Healthcare System, Palo Alto, CA 94025, USA.
authors.forename: Zurab
authors.initials: Z
authors.lastname: Siprashvili
authors.forename: Jason A
authors.initials: JA
authors.lastname: Reuter
authors.forename: Paul A
authors.initials: PA
authors.lastname: Khavari
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism / Q000627:therapeutic use; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism / Q000627:therapeutic use; D012867:Skin / Q000166:cytology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D010455:Peptides; D011506:Proteins; C055324:phospholipase A2-activating protein; C494021:transporter peptide HGH6; D001616:beta-Galactosidase; D020169:Caspases