Cell-Permeable Peptide Nucleic Acid Designed to Bind to the 5‘-Untranslated Region of E-cadherin Transcript Induces Potent and Sequence-Specific Antisense Effects

• Published in: Journal of the American Chemical Society Vol. 128; no. 50; pp. 16104 - 16112
• Main Authors: Dragulescu-Andrasi, Anca, Rapireddy, Srinivas, He, Gaofei, Bhattacharya, Birendra, Hyldig-Nielsen, Jens J, Zon, Gerald, Ly, Danith H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.12.2006; Amer Chemical Soc
• Subjects: Analytical, structural and metabolic biochemistry; Base Sequence; Biological and medical sciences; Cadherins - genetics; Carbohydrates. Nucleosides and nucleotides; Cell Line, Tumor; Cell Membrane Permeability - drug effects; Cell Survival - drug effects; Chemistry; Chemistry, Multidisciplinary; Dna, deoxyribonucleoproteins; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; General and physical chemistry; Humans; Nucleic acids; Nucleosides, nucleotides and oligonucleotides; Oligonucleotides, Antisense - chemistry; Oligonucleotides, Antisense - genetics; Oligonucleotides, Antisense - pharmacology; Oligonucleotides, Antisense - toxicity; Organic chemistry; Peptide Nucleic Acids - chemistry; Peptide Nucleic Acids - genetics; Peptide Nucleic Acids - pharmacology; Peptide Nucleic Acids - toxicity; Physical Sciences; Preparations and properties; Science & Technology; Sensitivity and Specificity; Transcription, Genetic - genetics; PNA; HUMAN-DISEASE; INHIBITION; MESSENGER-RNA; DNA; GENE-EXPRESSION; ANTIMICROBIAL PEPTIDES; BETA-CATENIN; OLIGONUCLEOTIDES; DELIVERY; Human; Vertebrata; Mammalia; Gene; Nucleotide; Guanidines; Peptide nucleic acid; Gene expression; Oligomer; Antisense oligonucleotide; Nucleic acid; Protein
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja063383v

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.