PNA as a potential modulator of COL7A1 gene expression in dominant dystrophic epidermolysis bullosa: a physico-chemical studyElectronic supplementary information (ESI) available. See DOI: 10.1039/c3mb70283a

• Main Authors: Amato, Jussara, Stellato, Marco Ignazio, Pizzo, Elio, Petraccone, Luigi, Oliviero, Giorgia, Borbone, Nicola, Piccialli, Gennaro, Orecchia, Angela, Bellei, Barbara, Castiglia, Daniele, Giancola, Concetta
• Format: Article
• Language: English
• ISSN: 1742-206X; 1742-2051
• DOI: 10.1039/c3mb70283a

Dominant diseases are single gene disorders occurring in the heterozygous state. The mutated allele exerts a dominant effect because it produces an abnormal polypeptide that interferes with the function of the normal allele product. Peptide Nucleic Acids (PNAs) offer a route for a potential therapy for dominant diseases by selectively silencing the allele carrying the dominant mutation. Here, we have synthesized and studied the properties of a 15-mer PNA fully complementary to the site of the c.5272-38T>A sequence variation, which identifies a recurrent mutant COL7A1 allele causing dominant dystrophic epidermolysis bullosa (DDEB), a mendelian disease characterized by skin blistering. The PNA was conjugated with four lysine residues at the C-terminus and a fluorescent probe at the N-terminus. Physico-chemical results proved the formation of a stable, selective PNA/mutant-DNA heteroduplex in vitro . Intriguingly, when transfected into normal human fibroblasts, the PNA correctly localized in the cell nucleus. Our results open new therapeutic possibilities for patients with DDEB. PNA as a potential tool for selectively silencing the allele carrying the dominant mutation in dominant dystrophic epidermolysis bullosa disease.