Engineering and application of polymerases for synthetic genetics

•Synthetic genetics explores the properties of synthetic genetic polymers (XNAs).•New methods have allowed the discovery of polymerases for a wide range of XNAs.•These polymerases have allowed the isolation of XNA aptamers and catalysts (XNAzymes).•Novel base chemistry has yielded an organism with an expanded genetic alphabet.

Organic chemistry has systematically probed the chemical determinants of function in nucleic acids by variation to the nucleobase, sugar ring and backbone moieties to build synthetic genetic polymers. Concomitantly, protein engineering has advanced to allow the discovery of polymerases capable of utilizing modified nucleotide analogs. A conjunction of these two lines of investigation in nucleotide chemistry and molecular biology has given rise to a new field of synthetic genetics dedicated to the exploration of the capacity of these novel, synthetic nucleic acids for the storage and propagation of genetic information, for evolution and for crosstalk, that is, information exchange with the natural genetic system. Here we summarize recent progress in synthetic genetics, specifically in the design of novel unnatural basepairs to expand the genetic alphabet as well as progress in engineering polymerases capable of templated synthesis, reverse transcription and evolution of synthetic genetic polymers.

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