Progress in developing PNA as a gene-targeted drug

Peptide nucleic acid (PNA) is a DNA mimic in which the nucleobases are attached to a pseudopeptide backbone. This achiral, uncharged, and rather flexible peptide backbone permits more stable hybridization to DNA and RNA oligomers with uncompromised or even improved sequence selectivity. Additional advantages of PNA are stability against nucleases and proteases and convenient solid phase synthesis. At the RNA level, PNA can be targeted to mRNA to block protein synthesis in an antisense strategy. PNA can also be targeted to the RNA component of ribonucleoproteins (RNPs) to inhibit their enzymatic activities. At the DNA level, the unique ability of PNA to bind DNA by duplex invasion can be used to arrest transcription within a gene sequence or to provide an artificial open complex to promote transcription. This review focuses on recent progress toward the development of PNA as a sequence-targeted drug.