Efficient transduction with scAAV2/5 in macaques with preexisting immunity to AAV8
| Monkey . | Weight, kg . | Primary exposure . | Pretreatment anti-AAV8 titers, relative units . | Pretreatment anti-AAV5 titers, relative units . | Transduction efficiency and immune response following administration of scAAV2/5-LP1-hFIXco . | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Route . | Stable hFIX level, % of normal . | hFIX biological activity, % of normal . | Transgene copy no. per diploid genome* . | Anti-hFIX antibodies . | Duration of expression, d . | |||||
| M8-sc | 5.9 | Wild-type AAV8 | 29 | 2 | IV | 11 ± 1 | 8 ± 3 | 31 | Yes | < 35 |
| M9-sc | 8.9 | Wild-type AAV8 | 32 | 2 | IV | 12 ± 2 | 8 ± 3 | 62 | No | > 271 |
| M3-sc | 5.5 | scAAV2/8 | 41 | 3 | IV | 35 ± 5 | 27 ± 4 | ND | No | > 187 |
| 328 | 7.5 | Wild-type AAV8 | 67 | 2 | MV | 8 ± 2 | 5 ± 2 | 29 | No | > 187 |
| Monkey . | Weight, kg . | Primary exposure . | Pretreatment anti-AAV8 titers, relative units . | Pretreatment anti-AAV5 titers, relative units . | Transduction efficiency and immune response following administration of scAAV2/5-LP1-hFIXco . | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Route . | Stable hFIX level, % of normal . | hFIX biological activity, % of normal . | Transgene copy no. per diploid genome* . | Anti-hFIX antibodies . | Duration of expression, d . | |||||
| M8-sc | 5.9 | Wild-type AAV8 | 29 | 2 | IV | 11 ± 1 | 8 ± 3 | 31 | Yes | < 35 |
| M9-sc | 8.9 | Wild-type AAV8 | 32 | 2 | IV | 12 ± 2 | 8 ± 3 | 62 | No | > 271 |
| M3-sc | 5.5 | scAAV2/8 | 41 | 3 | IV | 35 ± 5 | 27 ± 4 | ND | No | > 187 |
| 328 | 7.5 | Wild-type AAV8 | 67 | 2 | MV | 8 ± 2 | 5 ± 2 | 29 | No | > 187 |
Transgene copy number estimated by Southern blot analysis.
IV indicates peripheral vein delivery; ND, not done; MV, mesenteric vein delivery.