The XNA world: progress towards replication and evolution of synthetic genetic polymers

Life's diversity is built on the wide range of properties and functions that can be encoded in natural biopolymers such as polypeptides and nucleic acids. However, despite their versatility, the range of chemical functionalities is limited, particularly in the case of nucleic acids. Chemical modification of nucleic acids can greatly increase their functional diversity but access to the full phenotypic potential of such polymers requires a system of replication. Here we review progress in the chemical and enzymatic synthesis, replication and evolution of unnatural nucleic acid polymers, which promises to enable the exploration of a vast sequence space not accessible to nature and deliver ligands, catalysts and materials based on this new class of biopolymers.

► XNAs are nucleic acid polymers composed entirely of unnatural building blocks.
► Advances in nucleotide chemistry and polymerase engineering enable the synthesis and replication of XNAs.
► Synthesis and replication enable evolution of specific XNA aptamers.
► The exploration of XNA sequence space promises to deliver new ligands, catalysts and materials.