Table 1.

Alanine aminotransferase activity (I.U.) in mice receiving lentivirus

Mouse group Mouse strain N Vector transgenePackaging construct Vector dose (μg p24)+/− PH Day 1 (I.U.) Day 3 (I.U.)
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  
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  
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  hFIX  ΔR8  36  +  100 ± 13  51 ± 2  
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 transgenePackaging construct Vector dose (μg p24)+/− PH Day 1 (I.U.) Day 3 (I.U.)
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  
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  
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  hFIX  ΔR8  36  +  100 ± 13  51 ± 2  
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).

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