Hemophilia A dogs treated with AAV-cFVIII vectors via portal-vein injection
Animal name . | AAV serotype . | Sex . | Age . | Weight, kg . | Dose, vg/kg . | Duration of study, wk . | Peak FVIII level, mU/mL,*(% of normal) . | Steady-state FVIII level mU/mL,*% of normal (mean ± SEM) . | WBCT after treatment, min,†mean ± SEM . | FVIII DNA copy/diploid genome in live biopsy,‡mean ± SEM . |
|---|---|---|---|---|---|---|---|---|---|---|
| Elisa§ | 2 | F | 7 m | 10 | 6 × 1012 | 171 | 269 (3.84) | 174 ± 6 (2.49 ± 0.09) | 5.22 ± 1.02 | 0.14 ± 0.13 |
| Angus | 2 | M | 1 y | 10.4 | 1.5 × 1013 | 62 | 64 (0.91) | 38 ± 5 (0.54 ± 0.07) | 6.37 ± 1.02 | ND |
| Vector | 2 | M | 8 m | 15.2 | 1.5 × 1013 | 96 | 256 (3.66) | 149 ± 11 (2.13 ± 0.16) | 5.85 ± 1.44 | 1.52 ± 0.28 |
| Junior§ | 2 | M | 1 y | 12.8 | 2.7 × 1013 | 139 | 351 (5.02) | 225 ± 9 (3.21 ± 0.13) | 4.96 ± 0.85 | 0.802 |
| Alexis | 6 | F | 1 y 8 m | 9.4 | 1.0 × 1013 | 73 | 598 (8.54) | 331 ± 27 (4.73 ± 0.39) | 4.21 ± 0.77 | 0.69 ± 0.06 |
| Morag | 6 | F | 6 m | 10.5 | 1.7 × 1013 | 46 | < 23 (< 0.33) | < 23 (< 0.33) | 6.29 ± 1.57 | 0.05 ± 0.01 |
| Maurizio | 6 | M | 1 y 2 m | 11.9 | 1.0 × 1013 | 44 | 227 (3.24) | 175 ± 9 (2.50 ± 0.13) | 4.57 ± 0.53 | 0.85 ± 0.28 |
| Floopers | 8 | F | 1 y | 11.2 | 1.0 × 1013 | 61 | 312 (4.46) | 177 ± 16 (2.53 ± 0.23) | 4.69 ± 1.16 | 0.80 ± 0.10 |
Animal name . | AAV serotype . | Sex . | Age . | Weight, kg . | Dose, vg/kg . | Duration of study, wk . | Peak FVIII level, mU/mL,*(% of normal) . | Steady-state FVIII level mU/mL,*% of normal (mean ± SEM) . | WBCT after treatment, min,†mean ± SEM . | FVIII DNA copy/diploid genome in live biopsy,‡mean ± SEM . |
|---|---|---|---|---|---|---|---|---|---|---|
| Elisa§ | 2 | F | 7 m | 10 | 6 × 1012 | 171 | 269 (3.84) | 174 ± 6 (2.49 ± 0.09) | 5.22 ± 1.02 | 0.14 ± 0.13 |
| Angus | 2 | M | 1 y | 10.4 | 1.5 × 1013 | 62 | 64 (0.91) | 38 ± 5 (0.54 ± 0.07) | 6.37 ± 1.02 | ND |
| Vector | 2 | M | 8 m | 15.2 | 1.5 × 1013 | 96 | 256 (3.66) | 149 ± 11 (2.13 ± 0.16) | 5.85 ± 1.44 | 1.52 ± 0.28 |
| Junior§ | 2 | M | 1 y | 12.8 | 2.7 × 1013 | 139 | 351 (5.02) | 225 ± 9 (3.21 ± 0.13) | 4.96 ± 0.85 | 0.802 |
| Alexis | 6 | F | 1 y 8 m | 9.4 | 1.0 × 1013 | 73 | 598 (8.54) | 331 ± 27 (4.73 ± 0.39) | 4.21 ± 0.77 | 0.69 ± 0.06 |
| Morag | 6 | F | 6 m | 10.5 | 1.7 × 1013 | 46 | < 23 (< 0.33) | < 23 (< 0.33) | 6.29 ± 1.57 | 0.05 ± 0.01 |
| Maurizio | 6 | M | 1 y 2 m | 11.9 | 1.0 × 1013 | 44 | 227 (3.24) | 175 ± 9 (2.50 ± 0.13) | 4.57 ± 0.53 | 0.85 ± 0.28 |
| Floopers | 8 | F | 1 y | 11.2 | 1.0 × 1013 | 61 | 312 (4.46) | 177 ± 16 (2.53 ± 0.23) | 4.69 ± 1.16 | 0.80 ± 0.10 |
ND indicates not determined.
FVIII activities in canine plasma were determined by Coatest and converted to percentage of normal canine FVIII activity of 7000 mU/mL. Pretreatment hemophilia A dogs had FVIII activity less than 1%.
Average WBCT from all time points measured after treatment with duplicate measurements at each time point. Pretreatment WBCT was 14 to 17 minutes.
Copy numbers of canine B-domain-deleted FVIII DNA in canine liver were determined by Southern blotting analysis.
Some data up to week 56 for Elisa and week 36 for Junior have been reported previously.2