Influence of protein transduction domains on intracellular delivery of macromolecules.
As the plasma membrane and blood-brain barrier selectively restrict the entry of most compounds into cells to < 500 Da, delivering macromolecules into cells was, until recently, little more than a goal. However, with significant effort to capitalise on therapeutic targets available in the post-genomic era, novel approaches for delivering therapeutic macromolecules are being rapidly developed. The discovery of small cationic peptides, termed peptide/protein transduction domains or cell-penetrating peptides, which cross biological membranes, has emerged as a venerable Trojan horse to transport large, biologically active molecules, such as peptides, proteins and oligonucleotides, into mammalian cells in vitro, as well as in preclinical models and clinical trials in vivo. This review discusses the implications of peptide/protein transduction domain-mediated delivery of macromolecules and their possible uses as important primary drug delivery agents.
Murriel
Christopher L
CL
Howard Hughes Medical Institute, Department of Cellular & Molecular Medicine, UCSD School of Medicine, La Jolla, CA 92093-0686, USA.
Dowdy
Steven F
SF
D000818:Animals; D002463:Cell Membrane Permeability; D016503:Drug Delivery Systems / Q000379:methods*; D015696:Gene Products, tat / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000008:administration & dosage*; D021381:Protein Transport; D014161:Transduction, Genetic
D015696:Gene Products, tat; D010455:Peptides