Eroshenko, N. & Church, G.M. Nat. Commun. 4, 2509 (2013).

Site-specific recombinases offer benefits for integrating transgenes into a genome because they avoid the random and potentially mutagenic nature of transposon or viral insertion and they do not stimulate the mutagenic repair processes that targeted nucleases can trigger. However, altering recombinases to recognize new sequences for gene delivery usually leads to nonspecific activity. Eroshenko and Church used theoretical modeling to show that reducing the binding cooperativity of the Cre recombinase dimer can improve binding accuracy without affecting the protein interface that determines the DNA-binding sequence. Using bacterial selection, they identified three Cre mutants that efficiently recombine loxP sites with fewer off-target events in the Escherichia coli genome.