| Literature DB >> 20420385 |
Edward V Wancewicz1, Martin A Maier, Andrew M Siwkowski, Klaus Albertshofer, Theodore M Winger, Andres Berdeja, Hans Gaus, Timothy A Vickers, C Frank Bennett, Brett P Monia, Richard H Griffey, Christopher J Nulf, Jiaxin Hu, David R Corey, Eric E Swayze, Garth A Kinberger.
Abstract
A peptide nucleic acid (PNA) targeting a splice junction of the murine PTEN primary transcript was covalently conjugated to various basic peptides. When systemically administered to healthy mice, the conjugates displayed sequence-specific alteration of PTEN mRNA splicing as well as inhibition of full length PTEN protein expression. Correlating activity with drug concentration in various tissues indicated strong tissue-dependence, with highest levels of activity observed in adipose tissue. While the presence of a peptide carrier was found to be crucial for efficient delivery to tissue, little difference was observed between the various peptides evaluated. A second PNA-conjugate targeting the murine insulin receptor primary transcript showed a similar activity profile, suggesting that short basic peptides can generally be used to effectively deliver peptide nucleic acids to adipose tissue.Entities:
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Year: 2010 PMID： 20420385 PMCID： PMC3072269 DOI： 10.1021/jm901489k
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446