Perspective: Solidifying the impact of cell-free synthetic biology through lyophilization

Highlights • Review of freeze-dried cell-free (FD-CF) systems. • FD-CF applications in sensing and portable biomanufacturing. • Challenges and opportunities ahead for the field.
Cell-free synthetic biology is an exciting and new branch in the field of synthetic biology. Based on in vitro transcription and translation systems, this application-focused domain builds on decades of cell-free biochemistry and protein expression to operate synthetic gene networks outside of cellular environments. This has brought new and perhaps even unexpected advantages. Chief among these is the ability to operate genetically encoded tools in a sterile and abiotic format. Recent work has extended this advantage by freeze-drying these cell-free systems into dried pellets or embedded paper-based reactions. Taken together, these new ideas have solved the longstanding challenge of how to deploy poised synthetic gene networks in a biosafe mode outside of the laboratory. There is significant excitement in the potential of this newfound venue and the community has begun to extend proof-of-concept demonstrations in important and creative ways. Here I explore these new efforts and provide my thoughts on the challenges and opportunities ahead for freeze-dried, cell-free synthetic biology.