Redesigning the Architecture of the Base Pair: Toward Biochemical and Biological Function of New Genetic Sets

Recognition of the nucleic acid bases within the DNA scaffold comprises the basis for transmission of genetic information, dictating protein and cell assembly, organismal development, and evolution. Driven in part by the need to test our current understanding of this information transfer, chemists have begun to design and synthesize nonnatural bases and base pair structures to mimic the function of DNA without relying on Nature's purine-pyrimidine base pair scaffold. Multiple examples have been recently described that self-assemble stably and sequence specifically in vitro, and some isolated unnatural base pairs can be replicated in vitro as well. Moreover, recent experiments with unnatural bases in bacterial cells have demonstrated surprisingly efficient reading of the chemical information. This suggests the future possibility of redesigning and replacing the chemical information of an evolving cell while retaining biological function.