Reinventing the Wheel: Synthetic Circular RNAs for Mammalian Cell Engineering

The circular RNA renaissance is upon us. Recent reports demonstrate applications of synthetic circular RNA molecules as gene therapies and in the production of biologics from cell-based expression systems. Circular RNAs are covalently closed loop RNA species that are formed naturally through noncolinear splicing of pre-mRNA. Although once thought to be noncoding artefacts from splicing errors, it is now accepted that circular RNAs are abundant and have diverse functions in gene regulation and protein coding in eukaryotes. Numerous reports have investigated circular RNAs in various diseases, but the promise of synthetic circular RNAs in the production of recombinant proteins and as RNA-based therapies is only now coming into focus. This review highlights reported uses of synthetic circular RNAs and describes methods for generating these molecules.