How custom polymerases are driving innovation in synthetic biology

Polymerases are the molecular machines of information transfer, yet their natural catalytic repertoire is largely restricted to DNA, RNA, and a limited set of chemically modified analogs. In response to this constraint, custom polymerases have emerged as powerful tools in the synthetic biology toolbox. Advances in polymerase engineering are unlocking access to RNA polymers generated by primer-extension rather than a promoter driven process as well as synthetic genetic polymers with unnatural backbone structures, collectively termed xeno-nucleic acids (XNAs). In this review, we highlight examples of how custom polymerases are redefining the chemical boundaries of genetic function and driving innovation across the fields of synthetic biology, biotechnology, and molecular medicine.