Weinberg, B.H. et al. Nat. Biotechnol. 35, 453–462 (2017).

Reprogramming cells to perform desired tasks or computations is a long-standing goal in synthetic biology. Although tools are being developed at a fast pace, engineering biocomputation circuits with multiple inputs and outputs in mammalian cells remains technically challenging. Weinberg et al. sought to address this challenge by developing Boolean logic and arithmetic through DNA excision (BLADE). BLADE is a general framework that uses site-specific recombinases for engineering complex logic circuits. These recombinases are powerful because they can function simultaneously as transcriptional activators and repressors. The researchers designed and tested over 100 different circuits and found that 96.5% functioned as intended without any additional optimization. The circuits represent a broad range of designs and can control CRISPR–Cas9 to regulate endogenous gene expression.