Expression of lysosomal enzymes deficient in Fabry and Gaucher diseases and Hurler and Hunter syndromes. Top panels of (A-D) Western blot detection of (A) α-galactosidase A, (B) α-l-iduronidase, (C) iduronate-2 sulfatase, and (D) acid β-glucosidase in liver lysates of mice 30 days after treatment with 3 × 1011 vg of AAV8-ZFN and AAV8 of the appropriate donor at the indicated ratio of 1:1 or 1:5 (see “Methods” section for details). Middle panels (A-D) PCR detection of bands consistent with homology directed (HDR) and homology independent (NHEJ) integration of donor at the albumin locus. Lower panels (A-D) Indel formation as measured by MiSeq sequencing (n = 3 mice per group). Each lane represents an individual mouse. LSD, lysosomal storage disease.