Comparison of novel delivery systems for antisense peptide nucleic acids

Peptide nucleic acids (PNAs) provide a powerful tool to study the mechanism of transcription and translation, an innovative strategy to regulate target gene expression. They have been successfully used in antisense technology, for their ability to specifically bind to messenger RNA (mRNA) targets and to inhibit translation of the target genes. However, unlike most of the DNA and RNA oligonucleotides, PNAs are poorly penetrated through the cell membrane, partially due to their uncharged property. To enhance the efficiency in PNA delivery, many strategies have been explored. We here compare the efficacy of three different delivery strategies for antisense PNA: 1) conjugation to hydrophobic peptides, 2) adsorption onto polymeric microspheres and 3) encapsulation in autologous erythrocytes. To this purpose, we designed and prepared PNA sequences able to inhibit the expression of macrophage enzymes involved in inflammatory process, i.e. nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) and tested their antisense activity in a murine macrophage cellular model. Both delivery through polymeric microspheres and encapsulation into erythrocytes allowed the antisense activity of unmodified PNAs at nanomolar concentration. Il lavoro è frutto di una stretta collaborazione tra gli autori appartenenti a tre diverse università italiane (Urbino, Genova e Piemonte Orientale) e 2 Enti di Ricerca (CNR, Bologna e Istitito Giannina Gaslini, Genova) Journal of Controlled Release con IF di 7.164. La rivista è in categoria Q1 in entrambe le categorie (CHEMISTRY, MULTIDISCIPLINARY e PHARMACOLOGY & PHARMACY) ove presente. Il lavoro ha ricevuto 19 citazioni e tra queste una review pubblicata su Nature Reviews Drug Discovery, Volume 9, Issue 10, October 2010, Pages 775-789.Targeting microRNAs in cancer: Rationale, strategies and challenges ( Review ).Garzon, R.A et al.