Lou, C. et al. Nat. Biotechnol. 30, 1137–1142 (2012).

In synthetic biology, genetic parts making up circuits should ideally function equally well in any context. Unfortunately, this is not the case, as a part's function is affected by genetic and cellular environment. Therefore, one cannot generalize the performance of any part but instead needs to test its efficacy in each new context. Various insulator elements inserted at the junction between parts have recently been shown to ameliorate context dependency; Lou et al. now add another. They showed that insertion of a ribozyme between two elements makes the output of a circuit dependent solely on the input and eliminates any interference by other sequences at the junction of the two parts. The presence of the ribozyme ensures tight control of a NOT gate designed with a variety of inducible promoters. Interference between parts in synthetic genetic circuits is a major challenge that needs to be addressed to make full use of the ever-increasing number of parts.