Genetic circuit

In synthetic biology, a genetic circuit is an engineered arrangement of genes, promoters and regulatory proteins or RNAs that processes signals inside a living cell. Inputs, such as a sugar, a drug or a change in temperature, alter the activity of regulators, which switch promoters on or off. The output is usually the production of a protein, for example a fluorescent reporter or an enzyme. The name borrows from electronics because circuits can be wired to perform logic, memory and timing.

Two landmark circuits built in E. coli and published in 2000 showed the idea could work. The genetic toggle switch used two repressors that shut off each other's genes, so cells settled in one of two stable states and could be flipped between them by a chemical signal. The repressilator linked three repressors in a ring, each blocking the next, which made fluorescence rise and fall in a regular rhythm. Since then, researchers have built logic gates, counters, pulse generators and biosensors, using repressors, CRISPR interference and DNA-flipping recombinases.

Design remains difficult. Parts behave differently depending on neighboring DNA, the host cell and growth conditions, gene expression is noisy, and circuits burden the cell's resources. Designers therefore tune promoters and ribosome binding sites and refine their designs over repeated build-and-test cycles.