Intracellular delivery of functional proteins via decoration with transporter peptides.
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.
Siprashvili
Zurab
Z
VA Palo Alto Healthcare System, Palo Alto, CA 94025, USA.
Reuter
Jason A
JA
Khavari
Paul A
PA
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
D002352:Carrier Proteins; D010455:Peptides; D011506:Proteins; C055324:phospholipase A2-activating protein; C494021:transporter peptide HGH6; D001616:beta-Galactosidase; D020169:Caspases