title: Cell targeting peptide conjugation to siRNA polyplexes for effective gene silencing in cardiomyocytes.
abstract: To deliver siRNA specifically to cardiomyocytes with a high transfection efficiency, primary cardiomyocyte-targeting (PCM) and/or cell-penetrating (Tat) peptides were incorporated into the siRNA. With the addition of plasmid DNA, these peptide-conjugated siRNAs were able to form compact and stable nanosized polyplex particles with bioreducible poly(CBA-DAH). The peptide-modified siRNA polyplexes enhanced the cellular uptake and the gene-silencing capacity of the siRNA in cardiomyocytes without significant immunogenicity or cytotoxicity. These findings demonstrate that the cell-targeting peptide and/or cell-penetrating peptide conjugation of siRNA may be a potentially important strategy for cell-specific gene therapy in gene-mediated disease states.
authors.affiliation: Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
authors.forename: Hye Yeong
authors.initials: HY
authors.lastname: Nam
authors.forename: Jaesung
authors.initials: J
authors.lastname: Kim
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: David A
authors.initials: DA
authors.lastname: Bull
mesh_terms: D002460:Cell Line; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D020868:Gene Silencing; D015316:Genetic Therapy; D006801:Humans; D008855:Microscopy, Electron, Scanning; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D057846:Cell-Penetrating Peptides; D011108:Polymers; D034741:RNA, Small Interfering