Journal of Nucleic Acids

Expansion of the Genetic Alphabet: Unnatural Nucleobases and their Applications

Publishing date
15 Feb 2013
Submission deadline
28 Sep 2012

1Department of Chemistry, Indian Institute of Technology Guwahati, Assam, Guwahati 781 039, India

2Department of Chemistry, University of Utah, Salt Lake City, UT, USA

3Department of Chemical Biology and Applied Chemistry, School of Engineering, Nihon University, Koriyama, Fukushima, Japan

4Department of Chemistry, Roy and Diana Vagelos Laboratories, University of Pennsylvania, PA, USA

Expansion of the Genetic Alphabet: Unnatural Nucleobases and their Applications


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 Prospective authors should submit an electronic copy of their complete manuscript through the journal Manuscript Tracking System at according to the following timetable:


  • Special Issue
  • - Volume 2012
  • - Article ID 718582
  • - Editorial

Expansion of the Genetic Alphabet: Unnatural Nucleobases and Their Applications

Subhendu Sekhar Bag | Jennifer M. Heemstra | ... | David M. Chenoweth
  • Special Issue
  • - Volume 2012
  • - Article ID 354549
  • - Research Article

Convenient and Scalable Synthesis of Fmoc-Protected Peptide Nucleic Acid Backbone

Trevor A. Feagin | Nirmal I. Shah | Jennifer M. Heemstra
  • Special Issue
  • - Volume 2012
  • - Article ID 230943
  • - Research Article

PCR Amplification and Transcription for Site-Specific Labeling of Large RNA Molecules by a Two-Unnatural-Base-Pair System

Michiko Kimoto | Rie Yamashige | ... | Ichiro Hirao
  • Special Issue
  • - Volume 2012
  • - Article ID 530963
  • - Review Article

Synthetic Nucleotides as Probes of DNA Polymerase Specificity

Jason M. Walsh | Penny J. Beuning
  • Special Issue
  • - Volume 2012
  • - Article ID 156035
  • - Research Article

Features of “All LNA” Duplexes Showing a New Type of Nucleic Acid Geometry

Charlotte Förster | André Eichert | ... | Jens P. Fürste
  • Special Issue
  • - Volume 2012
  • - Article ID 196845
  • - Research Article

Metal Ion Chelates as Surrogates of Nucleobases for the Recognition of Nucleic Acid Sequences: The Complex of 2,6-Bis(3,5-dimethylpyrazol-1-yl)purine Riboside

Sharmin Taherpour | Tuomas Lönnberg
Journal of Nucleic Acids
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