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 ra ther flexible peptide backbone permits more stable hybridization to DN A and RNA oligomers with uncompromised or even improved sequence selec tivity. Additional advantages of PNA are stability against nucleases a nd proteases and convenient solid phase synthesis. At the RNA level, P NA can be targeted to mRNA to block protein synthesis in an antisense strategy. PNA can also be targeted to the RNA component of ribonucleop roteins (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 artif icial open complex to promote transcription. This review focuses on re cent progress toward the development of PNA as a sequence-targeted dru g.