Efficient, continuous mutagenesis in human cells using a pseudo-random DNA editor

Here, we describe TRACE, a method that enables continuous, targeted mutagenesis in human cells using a cytidine deaminase fused to T7 RNA polymerase. TRACE induces high rates of mutagenesis over multiple cell generations in genes under the control of a T7 promoter integrated in the genome. Using TRACE in a MEK1 inhibitor resistance screen, we identified functionally correlated mutations.