Cell-Free Systems: A Proving Ground for Rational Biodesign

Abstract

Cell-free gene expression systems present an alternative approach to synthetic biology, where biological gene expression is harnessed inside non-living, in vitro biochemical reactions. Taking advantage of a plethora of recent experimental innovations, they easily overcome certain challenges for computer-aided biological design. For instance, their open nature renders all their components directly accessible, greatly facilitating model construction and validation. At the same time, these systems present their own unique difficulties, such as limited reaction lifetimes and lack of homeostasis. In this Perspective, I propose that cell-free systems are an ideal proving ground to test rational biodesign strategies, as demonstrated by a small but growing number of examples of model-guided, forward engineered cell-free biosystems. It is likely that advances gained from this approach will contribute to our efforts to more reliably and systematically engineer both cell-free as well as living cellular systems for useful applications.