Sequence-Specific Recognition of Double-Stranded DNA by Using Only PNAs in Parallel with Natural Nucleobases

The sequence-specific recognition of double-stranded DNA (dsDNA) is a key property for the control of DNA function. Peptide nucleic acid (PNA) can be utilised for the direct recognition of dsDNA via the formation of a unique invasion complex. Strand invasion by PNA induces local changes in the structure of dsDNA and is useful for the regulation of gene expression and genome editing. However, the fact that nucleobases modification is required for efficient invasion, has stymied the wide-spread application of PNA. Herein, we succeeded in the efficient recognition of target dsDNA sequences via formation of invasion complex by utilising only parallel-stranded and unmodified PNAs. This approach also streamlines synthesis by permitting the use of a peptide synthesiser rather than the manual synthesis we had been dependent upon for nucleobase-modified PNAs. Our new method also exhibited high sequence specificity and flexibility for target dsDNA sequences.