Development of cell-permeable peptide nucleic acid (PNA)

CARB 27

Danith H. Ly, dly@andrew.cmu.edu, Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213
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 cell-permeable, guanidine-based peptide nucleic acid (PNA) called GPNA. We show that GPNA 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.