PerspectiveMolecular Biology

Reprogramming the Genetic Code

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Science  27 Apr 2012:
Vol. 336, Issue 6080, pp. 428-429
DOI: 10.1126/science.1221761

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The genetic code provides rules by which a genome is decoded to produce proteins of defined amino acid composition and sequence. These rules, which specify 61 codons (triplets of nucleotides) that code for the 20 common amino acids, and 3 codons that signal the termination of protein synthesis, are near-universally conserved in living organisms. Despite conservation of this code and the translational machinery that enforces it, a growing body of work addresses the challenges in reprogramming the genetic code. Designer amino acids, created by synthetic chemistry, can now be incorporated into specific sites in proteins of interest in vitro, in cells, and most recently in a whole animal (see the figure). These routes to unnatural polymer synthesis and evolution are already facilitating the study of cellular processes including protein interactions, protein conformational changes, posttranslational modification biology, and the kinetics of protein transport and cell signaling with a new level of molecular precision (1). Emerging developments may allow the synthesis and evolution of new materials and therapeutics.