Peptide nucleic acid

I remember it like it was yesterday, even though it was more than 30 years ago. I was a graduate student at the University of Arizona (U.S.A.), sitting at my desk, eating lunch and perusing the latest issue of Science magazine. I came across an article about an intriguing new molecule called “polyamide nucleic acid” or PNA.^[1] (We now define PNA as “peptide nucleic acid,” which is a perfectly fine name, except that PNA technically is not a peptide, it is not found in the nucleus and it is not an acid!) My Ph.D. thesis research had nothing to do with nucleic acid chemistry, but I still found the article fascinating, as the authors—Peter Nielsen, Michael Egholm, Rolf Berg, and the late Ole Buchardt at the University of Copenhagen (Denmark)—reported the ability of PNA to bind complementary DNA targets via a novel strand-invasion mechanism. The exceptionally high affinity of PNA for its targets, its resistance to natural degradation pathways and its fidelity to the Watson–Crick rules for base pairing sparked an intense level of excitement in both the fundamental science and the applications of PNA that continues to this day. Reading that paper certainly triggered my interest in nucleic acids and motivated me to seek out a postdoctoral position in the field. Two years later, I joined the laboratory of Gary Schuster at the University of Illinois (U.S.A.) where, by way of a happy accident, I had the good fortune to begin working with PNA through collaboration with Peter Nielsen's laboratory. 29 years later, my lab continues to work with this amazing molecule and its descendants. That paper changed my life!

In this Special Collection of Biopolymers, we have gathered original research and review articles that highlight the ongoing evolution of PNA—both its structure and its applications. Backbone modifications that enhance affinity, nucleobase modifications that promote cell uptake, new applications in biosensing and self-assembly, and advances in targeting non-canonical structures, such as double-stranded RNA all demonstrate the versatility of PNA. While the original structure of PNA bedeviled researchers because of technical issues, for example aggregation, the next generation of PNAs have overcome these challenges. Moreover, the exploitation of PNA's peptide-like character via incorporation of amino acid side chains into the backbone, distinguishes PNA from other members of the nucleic acid alphabet soup, for example, LNA, that are more closely related to the natural biopolymers DNA and RNA.

We hope you enjoy reading these articles and that you will return from time to time as we plan to take advantage of the dynamic nature of a virtual Special Collection to add more contributions in the future. Who knows what is in store for PNA, but the seemingly endless varieties that chemists are producing and the innovative new applications that scientists and biotechnologists continue to develop give great optimism that the PNA universe will continue to expand from the Big Bang of the 1991 paper.