Alanine aminotransferase activity (I.U.) in mice receiving lentivirus
Mouse group . | Mouse strain . | N . | Vector transgene . | Packaging construct . | Vector dose (μg p24) . | +/− PH . | Day 1 (I.U.) . | Day 3 (I.U.) . |
---|---|---|---|---|---|---|---|---|
1 | C57B1/6 | 6 | hFIX | ΔR8.74 | 8 | − | 93 ± 6 | 50 ± 4 |
1 | C57B1/6 | 4 | hFIX | ΔR8.74 | 36 | − | 122 ± 9 | 52 ± 4 |
1 | C57B1/6 | 4 | hFIX | ΔR8.74 | 108 | − | 366 ± 20 | 64 ± 4 |
2 | C57B1/6 | 5 | hFIX | ΔR8.74 | 8 | + | 93 ± 6 | 48 ± 4 |
2 | C57B1/6 | 6 | hFIX | ΔR8.74 | 36 | + | 218 ± 80 | 51 ± 2 |
2 | C57B1/6 | 4 | hFIX | ΔR8.74 | 108 | + | 329 ± 23 | 68 ± 4 |
3 | C57B1/6 | 8 | hFIX | ΔR8.2 | 36 | − | 278 ± 34 | 62 ± 2 |
4 | C57B1/6 scid | 4 | hFIX | ΔR8.74 | 36 | − | 130 ± 28 | 51 ± 2 |
5 | C57B1/6 | 4 | hFIX | ΔR8 | 36 | + | 100 ± 13 | 51 ± 2 |
6 | C57B1/6 | 5 | N/A | N/A | N/A | + | 67 ± 7 | 48 ± 3 |
7 | C57B1/6 | 3 | hFVIII | ΔR8.74 | 140 | + | 402 ± 204 | 63 ± 2 |
Mouse group . | Mouse strain . | N . | Vector transgene . | Packaging construct . | Vector dose (μg p24) . | +/− PH . | Day 1 (I.U.) . | Day 3 (I.U.) . |
---|---|---|---|---|---|---|---|---|
1 | C57B1/6 | 6 | hFIX | ΔR8.74 | 8 | − | 93 ± 6 | 50 ± 4 |
1 | C57B1/6 | 4 | hFIX | ΔR8.74 | 36 | − | 122 ± 9 | 52 ± 4 |
1 | C57B1/6 | 4 | hFIX | ΔR8.74 | 108 | − | 366 ± 20 | 64 ± 4 |
2 | C57B1/6 | 5 | hFIX | ΔR8.74 | 8 | + | 93 ± 6 | 48 ± 4 |
2 | C57B1/6 | 6 | hFIX | ΔR8.74 | 36 | + | 218 ± 80 | 51 ± 2 |
2 | C57B1/6 | 4 | hFIX | ΔR8.74 | 108 | + | 329 ± 23 | 68 ± 4 |
3 | C57B1/6 | 8 | hFIX | ΔR8.2 | 36 | − | 278 ± 34 | 62 ± 2 |
4 | C57B1/6 scid | 4 | hFIX | ΔR8.74 | 36 | − | 130 ± 28 | 51 ± 2 |
5 | C57B1/6 | 4 | hFIX | ΔR8 | 36 | + | 100 ± 13 | 51 ± 2 |
6 | C57B1/6 | 5 | N/A | N/A | N/A | + | 67 ± 7 | 48 ± 3 |
7 | C57B1/6 | 3 | hFVIII | ΔR8.74 | 140 | + | 402 ± 204 | 63 ± 2 |
Three different packaging constructs were used to make the vector in this study: (1) integrase-defective (ΔR8); (2) with accessory proteins (vif/vpr/vpu/nef; ΔR8.2); and (3) without accessory proteins (ΔR8.74); n = number of animals used in each group. +/− PH indicates whether or not partial hepatectomy was performed 48 hours prior to portal vein injection of lentivirus. The different mouse groups (all mouse groups used C57B1/6 mice except group 4 which used C57B1/6 scid mice) measured for liver injury are as follows. Group 1: Mice were administered increasing doses of lentivirus (Δ8.74) from 8 (n = 5) to 36 (n = 4) and to 108 (n = 4) μg p24. Group 2: Mice were given an approximate 70% partial hepatectomy 48 hours prior to the administration of increasing doses of lentivirus (ΔR8.74) from 8 (n = 5) to 36 (n = 6) and to 108 μg p24 (n = 4). Group 3: Mice were given lentivirus containing four accessory genes (ΔR8.2; vif/vpr/vpu/nef ) at a dose of 36 μg p24. Group 4: C57B1/6 scid mice were given lentivirus (ΔR8.74) at a dose of 36 μg p24. Group 5: Mice were given a partial hepatectomy as in group 2, but they were injected with integrase-defective lentivirus (36 μg p24; ΔR8). Group 6: Mice were injected with vehicle solution (phosphate-buffered saline without calcium/magnesium; n = 5). Group 7: Mice were given a partial hepatectomy as in group 2 and then injected with 140 μg p24 lentivirus expressing B-domain deleted hFVIII (n = 3).