Efficient and Isoform-Selective Inhibition of Cellular Gene Expression by Peptide Nucleic Acids

Yinghui Liu, Dwaine A. Braasch, Christopher J. Nulf, David R. Corey

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Peptide nucleic acids (PNAs) are a potentially powerful approach for the recognition of cellular mRNA and the inhibition of gene expression. Despite their promise, the rules for using antisense PNAs have remained obscure, and antisense PNAs have been used sparingly in research. Here we investigate the ability of PNAs to be effective antisense agents inside mammalian cells, to inhibit expression of human caveolin-1 (hCav-1), and to discriminate between its α and β isoforms. Many human genes are expressed as isoforms. Isoforms may play different roles within a cell or within different tissues, and defining these roles is a challenge for functional genomics and drug discovery. PNAs targeted to the translation start codons for the α and β isoforms inhibit expression of hCav-1. Inhibition is dependent on PNA length. The potency and duration of inhibition by PNAs are similar to inhibition of gene expression by short interferring RNA (siRNA). Expression of the α isoform can be blocked selectively by a PNA. Cell proliferation is halted by inhibition of expression of both hCav-1 isoforms, but not by inhibition of the α hCav-1 isoform alone. Efficient antisense inhibition and selective modulation of isoform expression suggest that PNAs are versatile tools for controlling gene expression and dissecting the roles of closely related protein variants. Potent inhibition by PNAs may supply a "knock down" technology that can complement and "cross-check" siRNA and other approaches to antisense gene inhibition that rely on oligomers with phosphate or phosphorothioate backbone linkages.

Original languageEnglish (US)
Pages (from-to)1921-1927
Number of pages7
JournalBiochemistry
Volume43
Issue number7
DOIs
StatePublished - Feb 24 2004

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Efficient and Isoform-Selective Inhibition of Cellular Gene Expression by Peptide Nucleic Acids'. Together they form a unique fingerprint.

  • Cite this