FIGURE 1

Plasma IDUA activity and urine GAG in AAV-IDUA-treated mice. (A) AAV-IDUA plasmid pTRCA1, constructed as described in Materials and Methods. TR, AAV inverted terminal repeat; CMV/BA, CMV early enhancer/chicken -actin promoter; G, chicken -globin intron; IDUA, human -L-iduronidase cDNA; pA, bovine growth hormone polyadenylation signal. (B) Plasma IDUA activity in control-treated normal and affected MPS I littermates. One-day-old mice were injected via the superficial temporal vein with 10¹⁰ particles of control AAV-gfp vector. Blood plasma was obtained as described in Materials and Methods and tested for IDUA activity at the indicated times after vector injection. () Animals 62, () 63, Idua ^+/+; () 37, () 38, Idua ^+/-; () 36, 39, 65, 70, Idua ^-/-. (C) Plasma IDUA activity in vTRCA1-treated Idua ^-/- animals. One-day-old mice were injected via the superficial temporal vein with 10¹⁰ particles of vTRCA1. Blood plasma was obtained as described in Materials and Methods and tested for IDUA activity at the indicated times after vector injection. () Animals 26, () 27, () 28, () 30, () 31, () 33, () 35, () 41, () 44, () 45. () Mean IDUA activity. (D) Urine GAG. GAG, glycosaminoglycan; cr, creatinine. Beginning 1 month after vector injection, urine was collected and GAG was quantitated as described in Materials and Methods. For Idua ^-/- and Idua ^+/-, graph depicts the mean (+SD) of n = 4 animals. For vTRCA1-treated Idua ^-/- animals, graph depicts the mean (+SD) of n = 9 animals through month 3 and depicts the mean of n = 7 animals for months 4 and 5. ^* P < 0.05 between Idua ^-/- and vTRCA1-treated Idua ^-/- animals. ^**P < 0.005 between Idua ^-/- and vTRCA1-treated Idua ^-/- animals. Idua ^+/-, untreated heterozygous controls; Idua ^-/-, AAV-gfp-treated homozygous null controls.