News Finding: In all tested peripheral organs, treatment at the highest dose resulted in greater than 95% reduction in glycosaminoglycan (GAG) substrate levels.
Paper Finding: All ZFN+donor groups exhibited dose-dependent IDS activity levels in the liver at 1 month (mean values of 265, 1,756, and 2,479 nmol/ hr/mg for the low-, mid-, and high-dose groups, respectively; Figure 3A) and 4 months (519, 1,696, and 5,355 nmol/hr/mg protein for the low-, mid-, and high-dose groups, respectively; Figure 3B ) post-treatment.
News Context: Enzyme expression in liver cells reached levels greater than 200-fold higher than in wild-type mice. In all tested peripheral organs, treatment at the highest dose resulted in greater than 95% reduction in glycosaminoglycan (GAG) substrate levels. Importantly, treatment with Sangamo's genome editing therapy at the highest dose level also prevented the development of neurocognitive deficit in the young MPS II model mice, as measured by the Barnes Maze test.
Paper Context: Detection of hIDS protein thus required the presence of both ZFNs and the hIDS donor. All ZFN+donor groups exhibited dose-dependent IDS activity levels in the liver at 1 month (mean values of 265, 1,756, and 2,479 nmol/ hr/mg for the low-, mid-, and high-dose groups, respectively; Figure 3A) and 4 months (519, 1,696, and 5,355 nmol/hr/mg protein for the low-, mid-, and high-dose groups, respectively; Figure 3B ) post-treatment. The levels of IDS activity in all three ZFN+donor groups were significantly higher than control MPS II mice and were 20-, 66-, and 207-fold higher than levels found in wild-type mice at 4 months ( Figure 3B ).