The decoy approach against nuclear factor kB (NF-kB) is a useful tool to alter NF-kB dependent gene expression using synthetic oligonucleotides (ODNs) carrying NF-kB specific cis-elements. Unfortunately, ODNs are not stable and need to be extensively modified to be used in vivo or ex vivo. We have previously evaluated the possible use of peptide nucleic acids (PNAs) as decoy molecules. The backbone of PNAs is composed of N-(2-aminoethyl)glycine units, rendering these molecules resistant to both nucleases and proteases. We found that the binding of NF-kB transcription factors to PNAs was either very low (binding to PNA–PNA hybrids) or exhibited low.