Figure 1


Figure 1: Novel tyrosine-mutant AAV2 vectors. (A) The position of the 7 surface-exposed tyrosine residues on the AAV2 capsid surface, Y252, Y272, Y444, Y500, Y700, Y704, and Y730, are indicated by the arrows. Site-directed mutations of these tyrosine residues to phenylalanine residues (tyrosine-phenylalanine, Y-F) were performed and tyrosine-mutant capsid scAAV2-EGFP vectors were generated. (B) AAV2-mediated transgene expression in HeLa cells following transduction with tyrosine-mutant scAAV2-EGFP vectors. (C) Quantitative analyses of the transduction efficiency. P<0.01 vs. WT scAAV2-EGFP. (D) AAV2-mediated transduction of hepatocytes from normal C57BL/6 mice injected via tail vein with tyrosine-mutant capsid scAAV2-EGFP vectors. (E) Quantitative analyses of AAV2 transduction efficiency. P<0.01 vs. WT scAAV2-EGFP. (F) Comparative analyses of the WT or Y730F ssAAV2-ApoE/hAAT-hF.IX vector-mediated transduction efficiency in hepatocytes in mice in vivo. Human F.IX (hF.IX) expression in plasma as a function of time after injection of 1×10¹¹ viral particles/animal in BALB/c and C3H/HeJ mice via tail vein (tv), and 1×10¹⁰ viral particles/animal in C57BL/6 mice via tail vein (tv) or portal vein (pv). Fold-increase of hF.IX peak levels of Y730F vectors compared to the WT capsid vectors is indicated for each panel. [Proc. Natl. Acad. Sci., USA, 105: 7827-7832, 2008]

Figure 1: Novel tyrosine-mutant AAV2 vectors. (A) The position of the 7 surface-exposed tyrosine residues on the AAV2 capsid surface, Y252, Y272, Y444, Y500, Y700, Y704, and Y730, are indicated by the arrows. Site-directed mutations of these tyrosine residues to phenylalanine residues (tyrosine-phenylalanine, Y-F) were performed and tyrosine-mutant capsid scAAV2-EGFP vectors were generated. (B) AAV2-mediated transgene expression in HeLa cells following transduction with tyrosine-mutant scAAV2-EGFP vectors. (C) Quantitative analyses of the transduction efficiency. *P<0.01 vs. WT scAAV2-EGFP. (D) AAV2-mediated transduction of hepatocytes from normal C57BL/6 mice injected via tail vein with tyrosine-mutant capsid scAAV2-EGFP vectors. (E) Quantitative analyses of AAV2 transduction efficiency. *P<0.01 vs. WT scAAV2-EGFP. (F) Comparative analyses of the WT or Y730F ssAAV2-ApoE/hAAT-hF.IX vector-mediated transduction efficiency in hepatocytes in mice in vivo. Human F.IX (hF.IX) expression in plasma as a function of time after injection of 1×10¹¹ viral particles/animal in BALB/c and C3H/HeJ mice via tail vein (tv), and 1×10¹⁰ viral particles/animal in C57BL/6 mice via tail vein (tv) or portal vein (pv). Fold-increase of hF.IX peak levels of Y730F vectors compared to the WT capsid vectors is indicated for each panel. [Proc. Natl. Acad. Sci., USA, 105: 7827-7832, 2008]