Nucleic acids are essential biomolecules that encode the complex information necessary for life. Specific pairing of A with T (or U) and C with G during polymerase-mediated replication and transcription is the basis of the genetic code. However, why DNA and RNA each use only four bases remains one of the grand mysteries of biology. It was this question, coupled with the exciting possibility of generating DNA and RNA with enhanced functional abilities that led Alex Rich in 1962 to propose the concept of orthogonal base pairing between isoG and isoC and inspired Professor Steven A. Benner in the late 1980s to expand the genetic alphabet from four to six letters. In 1994, Professor Eric T. Kool opened a new functional dimension with the creation of nonhydrogen bonded unnatural nucleobase surrogates. Expansion of the genetic alphabet has increased the functional potential of DNA, for example, by enabling site directed oligonucleotide labeling and in vitro selections with oligonucleotides having increased chemical diversity. Translation of an expanded DNA alphabet into RNA is a challenging task, but one which has potential to give rise to semisynthetic organisms and increased biodiversity. Given the recent growth in research aimed at expanding the genetic alphabet, we feel it is an appropriate time to devote a special issue of Journal of Nucleic Acids to showcasing this research and the new technologies that it has enabled.

This special issue will focus on the synthesis and application of unnatural nucleobases/base pairs having novel properties. We invite authors to submit their original research works as well as review articles on recent advances in the field. Potential topics include, but are not limited to:

• Design and synthesis of unnatural nucleosides and nucleic acids
• PCR amplification of unnatural nucleotides
• Artificially expanded genetic information systems
• Structure and function of DNA/RNA with modified nucleobases
• Expanded genetic alphabet in the RNA world
• In vitro selections using an expanded genetic alphabet
• Nucleic acid detection using unnatural/modified nucleobases
• Use of modified nucleic acids in diagnostics, sensors, and nanotechnology
• DNA-mediated charge transfer involving modified nucleobases

Before submission authors should carefully read over the journal's Author Guidelines, which are located at http://www.hindawi.com/journals/jna/guidelines/. Prospective authors should submit an electronic copy of their complete manuscript through the journal Manuscript Tracking System at http://mts.hindawi.com/ according to the following timetable: