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Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Peptide Nucleic Acids (PNA)-DNA Chimeras Targeting Transcription Factors as a Tool to Modify Gene Expression

Author(s): M. Borgatti, A. Finotti, A. Romanelli, M. Saviano, N. Bianchi, I. Lampronti, E. Lambertini, L. Penolazzi, C. Nastruzzi, C. Mischiati, R. Piva, C. Pedone and R. Gambari

Volume 5, Issue 8, 2004

Page: [735 - 744] Pages: 10

DOI: 10.2174/1389450043345155

Price: $65

Abstract

Peptide nucleic acids (PNAs)-DNA chimeras have been recently described as DNA mimics constituted of a part of PNA and of a part of DNA. We have demonstrated that double stranded molecules based on PNA-DNA chimeras bind to transcription factors in a sequence-dependent manner. Accordingly, these molecules can be used for transcription factor decoy (TFD) pharmacotherapy. Effects of double stranded PNA-DNA chimeras targeting NF-kappaB and Sp1 were determined on in vitro cultured human cells and were found to be comparable to those observed using double-stranded DNA decoys. The TFD molecules based on PNA-DNA chimeras can be further engineered by addition of short peptides facilitating cell penetration and nuclear localization. Therefore, these engineered molecules could be of great interest for in vivo experiments for non-viral gene therapy of a variety of diseases, including neoplastic and viral diseases, for which the TFD approach has been already demonstrated as a very useful strategy.

Keywords: transcription, decoy, delivery, gene therapy, peptide-nucleic acids


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