Biodistribution of AAV8-hFIX vector DNA in rhesus macaques 6 months following direct hepatic artery injection
Macaque no. . | Vector dose, vg/kg . | Preexisting AAV8 NAB titer . | hFIX DNA copy/diploid genome* . | . | . | . | . | . | . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | . | . | Heart . | Kidney . | Liver . | Lung . | Spleen . | Testis . | Thymus . | ||||||
| Naive | 0 | NA | 0.0001 | 0.0000 | 0.0006 | 0.0000 | 0.0000 | 0.0001 | 0.0001 | ||||||
| R1 | 5 × 1012 | < 1:1 | 0.0002 | 0.0001 | 0.7606 | 0.0001 | 0.4566 | 0.0000 | 0.0003 | ||||||
| R2 | 5 × 1012 | < 1:1 | 0.0178 | ND | 4.7552 | 0.0021 | 0.0376 | 0.0017 | 0.0003 | ||||||
| R3 | 5 × 1012 | < 1:1 | 0.0342 | 0.0993 | 15.8653 | 0.0012 | 0.3650 | 0.0030 | 0.0002 | ||||||
| R4 | 5 × 1012 | < 1:1 | 0.0135 | 0.0189 | 6.6727 | 0.0001 | 1.9020 | 0.0167 | 0.0002 | ||||||
| R5 | 5 × 1012 | < 1:1 | 0.0038 | 0.0127 | 5.8211 | 0.0030 | 0.0735 | 0.0003 | 0.0000 | ||||||
| R6 | 5 × 1012 | < 1:1 | 0.0282 | 0.0213 | 5.7351 | 0.0062 | 0.1504 | 0.0022 | 0.0000 | ||||||
| R10 | 5 × 1012 | 1:5 | ND | 0.0001 | 0.1566 | 0.0000 | 0.0191 | 0.0002 | 0.0000 | ||||||
| R12‡ | 2 × 1013† | < 1:1 | 0.0807 | 0.0393 | 1.0671 | 0.0706 | 0.1626 | 0.0170 | 0.0200 | ||||||
| R14§ | 2 × 1013† | < 1:1 | 0.1442 | 0.1233 | 3.7224 | 0.0790 | 0.5691 | 0.0189 | 0.0000 | ||||||
Macaque no. . | Vector dose, vg/kg . | Preexisting AAV8 NAB titer . | hFIX DNA copy/diploid genome* . | . | . | . | . | . | . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | . | . | Heart . | Kidney . | Liver . | Lung . | Spleen . | Testis . | Thymus . | ||||||
| Naive | 0 | NA | 0.0001 | 0.0000 | 0.0006 | 0.0000 | 0.0000 | 0.0001 | 0.0001 | ||||||
| R1 | 5 × 1012 | < 1:1 | 0.0002 | 0.0001 | 0.7606 | 0.0001 | 0.4566 | 0.0000 | 0.0003 | ||||||
| R2 | 5 × 1012 | < 1:1 | 0.0178 | ND | 4.7552 | 0.0021 | 0.0376 | 0.0017 | 0.0003 | ||||||
| R3 | 5 × 1012 | < 1:1 | 0.0342 | 0.0993 | 15.8653 | 0.0012 | 0.3650 | 0.0030 | 0.0002 | ||||||
| R4 | 5 × 1012 | < 1:1 | 0.0135 | 0.0189 | 6.6727 | 0.0001 | 1.9020 | 0.0167 | 0.0002 | ||||||
| R5 | 5 × 1012 | < 1:1 | 0.0038 | 0.0127 | 5.8211 | 0.0030 | 0.0735 | 0.0003 | 0.0000 | ||||||
| R6 | 5 × 1012 | < 1:1 | 0.0282 | 0.0213 | 5.7351 | 0.0062 | 0.1504 | 0.0022 | 0.0000 | ||||||
| R10 | 5 × 1012 | 1:5 | ND | 0.0001 | 0.1566 | 0.0000 | 0.0191 | 0.0002 | 0.0000 | ||||||
| R12‡ | 2 × 1013† | < 1:1 | 0.0807 | 0.0393 | 1.0671 | 0.0706 | 0.1626 | 0.0170 | 0.0200 | ||||||
| R14§ | 2 × 1013† | < 1:1 | 0.1442 | 0.1233 | 3.7224 | 0.0790 | 0.5691 | 0.0189 | 0.0000 | ||||||
NA indicates not applicable; ND, not determined.
As determined by QPCR, according to a standard curve generated with linearized plasmid DNA pAAV-hFIX. The limit of detection is 8 × 10-5 copy/diploid genome. Endogenous macaque FIX DNA was not detected since the primer and probe are specific to hFIX spanning exons 5 and 6, excluding the intervening intron.
Biodistribution determined at 9 months following direct hepatic artery injection.
Without immunosuppressive treatment.
With immunosuppressive treatment.