Inteins are proteins that possess both endonuclease and self-splicing activity, allowing self excision and insertion at both the level of the gene and of the protein. Wood and coworkers (p. 889) have used a combination of rational design and an elegant genetic screen in Escherichia coli to engineer a mini-intein that lacks endonuclease activity, and is fine-tuned for use as a tool for recombinant protein purification.