The data shown here provide strong support for a ZFN-driven, in vivo gene-editing approach for the long-term treatment of peripheral symptoms of MPS I. This strategy is a broadly applicable platform approach, and we have previously demonstrated functional expression of the proteins deficient in hemophilia A and B, MPS II, Fabry disease, and Gaucher disease from the albumin locus following ZFN-mediated insertion.7 Here, ALB is linked to Fabry disease.