Cationic liposomes as delivery systems for double-stranded PNA-DNA chimeras exhibiting decoy activity against NF-kb transcription factors

Peptide nucleic acids (PNAs) have been recently proposed as useful mols. in pharmacogenetic therapy, esp. due to the fact that they show a very high stability with respect to DNA and RNA. However, PNAs are not efficient decoy mols., are characterized by negligible cell internalization and low soly. and are not suitable to be delivered by liposomes. With respect to the biol. activity of PNA-based mols., PDP deserve great consideration, due to the fact that they exhibit high levels of soly., and are expected to be resistant to proteinases and exonucleases. In this manuscript we detd. whether double-stranded mols. based on PNA-DNA chimeras contg. NF-kB binding sites, exhibit decoy activity against NF-kB transcription factors. In addn., we detd. whether they can be complexed by cationic liposomes. The results obtained demonstrated that hybrids based on PNA-DNA chimeras are powerful decoy mols. against NF-kB p52 transcription factor. In addn., we found that cationic liposomes can be proposed for in vitro delivery to target cells of these decoy mols. The results presented in this paper are thus of practical importance, since the simplicity and the versatility of the cationic liposome technol. have made cationic liposomes useful nonviral gene delivery systems for human gene therapy.