title: Cell-permeable peptide nucleic acid designed to bind to the 5'-untranslated region of E-cadherin transcript induces potent and sequence-specific antisense effects.
abstract: Establishing a general and effective method for regulating gene expression in mammalian systems is important for many aspects of biological and biomedical research. Herein we report the antisense activities of a cell-permeable, guanidine-based peptide nucleic acid (PNA) called GPNA. We show that a GPNA oligomer designed to bind to the transcriptional start-site of human E-cadherin gene induces potent and sequence-specific antisense effects and is less toxic to the cells than the corresponding PNA-polyarginine conjugate. GPNA confers its silencing effect by blocking protein translation. The findings reported in this study provide a molecular framework for designing the next generation cell-permeable nucleic acid mimics for regulating gene expression in live cells and intact organisms.
authors.affiliation: Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Anca
authors.initials: A
authors.lastname: Dragulescu-Andrasi
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rapireddy
authors.forename: Gaofei
authors.initials: G
authors.lastname: He
authors.forename: Birendra
authors.initials: B
authors.lastname: Bhattacharya
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Hyldig-Nielsen
authors.forename: Gerald
authors.initials: G
authors.lastname: Zon
authors.forename: Danith H
authors.initials: DH
authors.lastname: Ly
mesh_terms: D001483:Base Sequence; D015820:Cadherins / Q000235:genetics*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity; D020135:Peptide Nucleic Acids / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D015820:Cadherins; D016376:Oligonucleotides, Antisense; D020135:Peptide Nucleic Acids