Therapeutic applications of cell-penetrating peptides.
Since the discovery over 15 years ago of a protein transcription factor that possessed the ability to cross the plasma membrane, cell-penetrating peptides (CPPs) have been evaluated for the ability to transport diverse cargoes into cells, tissues, and organs. Certain CPPs have been used for the intracellular delivery of information-rich molecules to modulate protein-protein interactions and thereby inhibit key cellular mechanisms of disease. The ability to introduce drugs into cells allows the conventional biodistribution of drugs to be altered in order to favorably impact toxicity, patient compliance, and other treatment factors. In this monograph, we present the current status and future prospects for the application of CPPs to the development of human therapeutics. We discuss some of the advantages and disadvantages of using CPPs in the in vivo setting, and review the current status of a number of preclinical and human clinical studies of CPP-mediated delivery of therapeutics. These include CPP-conjugated moieties directed against a growing variety of targets and disease areas, including cancer, cardiology, pain, and stroke. Our discussion focuses on those therapeutics that have been tested in humans, including a CPP conjugate for the treatment of acute myocardial infarction. The promising results obtained in a number of these studies indicate that CPPs may have an important role in the development of novel therapeutics.
KAI Pharmaceuticals, Inc, San Francisco, CA, 94080, USA.
Randolph M
RM
Johnson
Stephen D
SD
Harrison
Derek
D
Maclean
D000595:Amino Acid Sequence; D000818:Animals; D057846:Cell-Penetrating Peptides / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D002986:Clinical Trials as Topic; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008969:Molecular Sequence Data; D021381:Protein Transport
D057846:Cell-Penetrating Peptides; D004337:Drug Carriers