Summary of dogs with hemophilia B treated by intramesenteric vein or portal vein (E34) administration of AAV-(ApoE)4/hAAT-cFIX
| Animal (colony) . | Age* (mo) . | Weight* (kg) . | Total dose (vg) . | Dose/kg (vg/kg) . | PK deficiency . | WBCT (min) . | APTT (s) . | cFIX (ng/mL) . | cFIX activity (%) . |
|---|---|---|---|---|---|---|---|---|---|
| Brad† | 9 | 10.2 | 1.25 × 1013 | 1.2 × 1012 | No | 12 ± 2.5 | 29.5 ± 3.5 | 590 ± 150 | 8.5 ± 2 |
| (Auburn) | |||||||||
| Semillon† | 5.5 | 6.0 | 9.7 × 1012 | 1.6 × 1012 | No | 13.5 ± 4 | 35.5 ± 2 | 220 ± 65 | 5 ± 2.5 |
| (Auburn) | |||||||||
| Beech† | 12 | 10.5 | 3.6 × 1013 | 3.4 × 1012 | Yes | ≥ 10 | ≥ 36.2 | ≤ 2560 | ≤ 3 |
| (Auburn) | |||||||||
| E34‡ | 5 | 12.3 | 9.6 × 1012 | 8 × 1011 | No | 11 ± 2.5 | 32 ± 4.5 | 262 ± 92 | 5 ± 2.5 |
| (UNC) |
| Animal (colony) . | Age* (mo) . | Weight* (kg) . | Total dose (vg) . | Dose/kg (vg/kg) . | PK deficiency . | WBCT (min) . | APTT (s) . | cFIX (ng/mL) . | cFIX activity (%) . |
|---|---|---|---|---|---|---|---|---|---|
| Brad† | 9 | 10.2 | 1.25 × 1013 | 1.2 × 1012 | No | 12 ± 2.5 | 29.5 ± 3.5 | 590 ± 150 | 8.5 ± 2 |
| (Auburn) | |||||||||
| Semillon† | 5.5 | 6.0 | 9.7 × 1012 | 1.6 × 1012 | No | 13.5 ± 4 | 35.5 ± 2 | 220 ± 65 | 5 ± 2.5 |
| (Auburn) | |||||||||
| Beech† | 12 | 10.5 | 3.6 × 1013 | 3.4 × 1012 | Yes | ≥ 10 | ≥ 36.2 | ≤ 2560 | ≤ 3 |
| (Auburn) | |||||||||
| E34‡ | 5 | 12.3 | 9.6 × 1012 | 8 × 1011 | No | 11 ± 2.5 | 32 ± 4.5 | 262 ± 92 | 5 ± 2.5 |
| (UNC) |
Results for WBCT, aPTT, cFIX plasma levels as determined by ELISA, and cFIX activity as percentage of activity in normal dog plasma are average values (± 1 SD) for weeks 3 to 86 (Brad), weeks 3 to 42 (Semillon), or weeks 3 to 48 (E34) after vector administration. Values for Beech represent peak levels before inhibitor development. The ranges for coagulation times in normal dogs are 6 to 10 minutes (WBCT), 1 to 2 minutes (ACT), and 18 to 20 seconds (aPTT). In hemophilia B dogs they are more than 60 minutes (WBCT), more than 4 minutes (ACT), and more than 60 seconds (aPTT).
Age and weight at time of vector administration.
Male hemophilia B dogs of Auburn colony with FIX null mutation.
Female hemophilia B dog of UNC-Chapel Hill colony with FIX missense mutation.