The capacity of short PNAs to selectively bind specifically-targeted nucleic acid sequences, either by Watson-Crick base pairing or by triple-helix formation involving Hoogstein bonding, confers on them an enormous potential to interfere with nucleic acid information processing. Their incapacity of forming a suitable substrate for RNase H has often been considered a major limiting factor to their capacity to regulate gene expression. It is now clear, however, that judicious targeting can lead to the disruption of specific and crucial steps of nucleic acid information processing. This is particularly true of many of the mechanisms that are specific to viruses.