PNA as a potential modulator of COL7A1 gene expression in dominant dystrophic epidermolysis bullosa: a physico-chemical study.

[dystrophic epidermolysis bullosa]

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 -38 T >A sequence variation , which identifies a recurrent mutant COL 7 A 1 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 .