Table 3.
Bleeding frequencies in haemophilia A and haemophilia B dogs from published gene transfer studies.
| Dog | A/B | M/F | Vector | Route | Vector dose | Months follow-up | WBCT (min) | cFIX, cFVIII, or cFVIIa | Bleeds per year post gene transfer |
|---|---|---|---|---|---|---|---|---|---|
| 1. Herzog et al. 1999 [17] | |||||||||
| B45 | B | M | AAV-2-CMV-cFIX | i.m. | 1.3 ×1011 vp kg−1 | 16 | 20 ± 5 | 2.6 ± 0.7 | 0.3 |
| B46 | B | M | AAV-2-CMV-cFIX | i.m. | 1.1 ×1012 vp kg−1 | 14 | 20 ± 2.5 | 12 ± 2 | 1.8 |
| B93 | B | M | AAV-2-CMV-cFIX | i.m. | 3 ×1012 vp kg−1 | 12 | 15 ± 1.5 | 21 ± 2 | 0.3 |
| B48 | B | F | AAV-2-CMV-cFIX | i.m. | 3.4 ×1012 vp kg−1 | 12.5 | 16 ± 1.5 | 17 ± 2 | 0.2 |
| B85 | B | F | AAV-2-CMV-cFIX | i.m. | 8.5 ×1012 vp kg−1 | 11 | 17 ± 2 | 69 ± 6 | 0.5 |
| 2. Snyder et al. 1999 [18] | |||||||||
| B84 | B | F | AAV2-MFG-cFIX | PV | 2 ×1012 vp | 4 | 12–20 | 30–95 | 0 |
| B89 | B | M | AAV2-MFG-cFIX | PV | 2 ×1012 vp | 4 | 10–25 | 10–45 | 0.25 |
| 3. Mount et al. 2002 [19] | |||||||||
| E34 | B | F | AAV2-hAAT-cFIX | PV | 8.0 ×1011 vg kg−1 | 12 | 11 ± 2.5 | 262 ± 92 | 0.1 |
| 4. Arruda et al. 2004 [20] | |||||||||
| E57 | B | M | AAV-1 CMV PK9 | i.m. | 2.4 ×1011 vg kg−1 | 33 | 18.1* | 104 | 0.1 |
| E35 | B | F | AAV-1-CMV-PK9 | i.m. | 1 ×1012 vg kg−1 | 9.5 | 19.1* | 87 | 0.1 |
| D31 | B | F | AAV-2-CMV-cFIX | i.m. | 8.5 ×1012 vg kg−1 | 27 | 18.4 | 39 | 0.02 |
| D32 | B | M | AAV-2-CMV-cFIX | i.m. | 5.6 ×1012 vg kg−1 | 30.5 | 17 | 40 | 0.1 |
| B14 | B | M | AAV-2-CMV-cFIX | i.m. | 1.1 ×1013 vg kg−1 | 39.5 | 21.2* | 30 | 0.1 |
| 5. Arruda et al. 2005 [21] | |||||||||
| F57 | B | M | AAV2-CMV-cFIX | ILP | 1.7 ×1012 vg kg−1 | 27 | 18.2 | 260 ± 52 | 0.04 |
| D99 | B | F | AAV2-CMV-cFIX | ILP | 3.7 ×1012 vg kg−1 | 39 | 13.9 | 730 ± 60 | 0.08 |
| H08 | B | M | AAV2-CMV-cFIX | ILP | 3.0 ×1012 vg kg−1 | 8 | 19.9 | 210 ± 16 | 0.1 |
| E60 | B | F | AAV2-CMV-cFIX | ILP | 3.9 ×1012 vg kg−1 | 10 | 16.3 | <1–100 | 0.3 |
| E59 | B | F | AAV2-CMV-cFIX | i.v. | 2.9 ×1012 vg kg−1 | 37 | 16.8 | 31–78 | 0.03 |
| 6. Xu et al. 2005 [16] | |||||||||
| H22 | A | F | RVhAAT-cFVIII-WPRE | i.v. | ~0.8 ×1010 TU kg−1 | 16 | 9.7 | 101 ± 4% | 0 |
| H18 | A | M | RVhAAT-cFVIII-WPRE | i.v. | ~0.8 ×1010 TU kg−1 | 16 | 9.8 | 129 ± 7% | 0 |
| 7. Margaritis et al. 2009 [2] | |||||||||
| J10 | B | M | AAV8-hAAT-cFVIIa | PV | 2.06 ×1013 vg kg−1 | 34 | 37.8 | ≤0.5 | 0 |
| J55 | A | M | AAV8-hAAT-cFVIIa | PV | 6.25 ×1013 vg kg−1 | 18 | 26.2 | 1.3–2.6 | 0 |
| J57 | A | F | AAV8-hAAT-cFVIIa | PV | 1.25 ×1014 vg kg−1 | 15 | 23.9 | 1.3–2.6 | 0 |
| E66 | A | M | AAV8-hAAT-cFVIIa | PV | 1.25 ×1014 vg kg−1 | 12 | 29.8 | 1.3–2.6 | 0 |
A/B, haemophilia A or haemophilia B genotype; M/F, male/female; Vector: AAV-n, adeno-associated virus (and n refers to serotype number); cFVIIa, canine factor VIIa; cFVIII, canine factor VIII; cFIX, canine factor IX; CMV, cytomegalovirus promoter; hAAT, human alpha-1-antitrypsin promoter; MFG, viral MFG promoter; RV, retrovirus; WPRE, woodchuck post-transcriptional regulatory element; Route: ILP, isolated limb perfusion; i.m., intramuscular; i.v., intravenous; PV, portal vein; Vector dose: TU, transducing units; vg, vector genomes; vp, vector particles; WBCT, whole blood clotting time.
cFIX in ng mL−1 (in 1, 2, 3, 4 and 5), cFVIII as percentage of normal (in 6), or cFVIIa μg mL−1 (in 7).
Values before these dogs developed inhibitory antibodies to canine FIX at which time their WBCT was >60.