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The two Mikes launched the creation of Nucleic Acids in Chemistry and Biology in 1986 to meet the pressing need for a single volume that integrated the chemistry and biology of nucleic acids. We delivered the 1st edition of Nucleic Acids in Chemistry and Biology in 1990, enjoying strong support from the editors and publishers of NAR. It was so very well received that it led to a 2nd edition (2E) in 1996, revised and rewritten largely by the same team of international experts. That edition was reprinted, but the passage of ten years and the still-growing demand for this book called for a new edition – driven firstly by the unabated expansion in the chemistry and biology of nucleic acids and secondly by the fact that the 2nd edition was a sell-out – with second-hand copies available on the internet at a handsome premium!

For the 3rd edition (3E), we expanded the editorial team with two younger colleagues, David Loakes and David Williams, changed publishers to the Royal Society of Chemistry and doubled a refreshed team of authors to provide scholarly delivery for that new, expanded edition. It dealt fully with recent advances – complete sequences of the human and numerous lesser genomes, the veritable explosion in the chemistry and biology of RNA and the many exciting crystal and nuclear magnetic resonance (NMR) structures of nucleic acids and their protein complexes – which it highlighted with Venki Ramakrishnan's structure of the ribosome on its cover. The 3rd edition proved effective as a teaching resource at every level of study and as an initiation into the molecular basis of nucleic acids science. At the same time, it succeeded in reaching out to senior scientists in many disciplines and world-class laboratories. We proudly possess a treasured, unique copy autographed by Jennifer Doudna: “Mike, Thanks for another wonderful book!”

The 4th edition (4E) of our book had to encompass the progress and new discoveries of a fifteen-year gap! To deliver the complexity of advances in nucleic acids technology, the huge expansion of new targets for their application, and the awesome success of their achievements demanded nothing less than a total overhaul of Nucleic Acids in Chemistry and Biology. The two Mikes began by addressing the overriding necessity of expanding the editorial group to embrace experts in biophysics and in biomedicine. Martin Egli gained his biophysical grounding in the groups of Jack Dunitz (ETHZ) and Alex Rich (MIT), had authored Chapter 2 in 3E, and accepted the invitation to edit 4E with alacrity. Wider searching identified Jonathan Watts, who had learned his nucleic acids chemistry with Masad Damha (McGill) and pharmacology with David Corey (UT Southwestern) and then globe-trotted until settling into the RNA Therapeutics Institute at UMass Medical School. Jon's acceptance completed our new editorial quartet.

Next, we overhauled the contents, balance, and order of presentation of the chapters. We increased chapter numbers from 11 to 15 (with the final chapter presented as an electronic online Appendix, too extensive to include in the printed book, available at We have given this volume totally new chapters on non-coding RNA, sequencing, therapeutics, aptamers and protein–RNA interactions, and we have doubled the size of Chapter 15 introducing physical and structural techniques. We trawled two continents for authors who possess the required teaching and research skills and identified an international team of 25 experts, 19 of them being new to this 4th edition: some turnover!

Above all, your four editors have endeavoured to maintain the quality of the earlier editions, each of which has been widely appreciated for easy readability, simplicity of exposition, clarity of illustration and uniformity of style. That has underpinned our efforts to deliver a 4th edition that once again fills the needs of students and new researchers from a breadth of scientific backgrounds, who seek to understand this great subject at a molecular level. Indeed, we know that Nucleic Acids in Chemistry and Biology has become the course book of choice in universities across three continents. Every chapter begins with an introduction aimed at a late undergraduate to early graduate level. That progresses to a more advanced level that gently but surely pushes towards the frontiers of current research (as of 2021) and finally concludes with a summary that offers a forward look to the challenges that lie ahead. We have made extensive use of illustrations to complement the text, we have virtually doubled the number of citations to original research publications and to major review articles (up to 2021), and we have made special efforts to smooth and meld the interface between cognate chapters and provide abundant cross-references to link them. Chapter 15, dedicated to the ever-advancing physical and structural techniques applied to nucleic acids, has been expanded in the authority of its authors, in scope and in size, albeit at the cost of presenting it as an electronic online appendix to enable the book to sustain its compact and accessible format. A strong feature is the expansion of the glossary designed to explain in uncomplicated language the meanings of some of the specialized, terminological argot of this amazing subject.

We commend this 4th edition into your hands to support your advancement in understanding of one of the greatest subjects in modern science. We hope it will give you as much pleasure in its perusal as we have enjoyed in its production.

Mike, Martin, Mike and Jon

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