Tissue biodistribution of canine FVIII transgene 4 months after injection
Dose and route of administration . | . | Tissue biodistribution, copies/cell . | . | . | . | . | . | . | . | . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | AAV serotype . | Liver . | Spleen . | Stomach . | Ileum . | Heart . | Lung . | Kidney . | Muscle . | Gonads . | ||||||||
| 1 × 1011 gc/vector/mouse | ||||||||||||||||||
| Portal vein | 8 (2 chains) | 9.60 | 0.01 | 0.02 | 0.00 | 0.26 | 0.01 | 0.07 | NA | 0.64 | ||||||||
| 8 (single chain) | 5.70 | 0.01 | 0.00 | 0.00 | 0.01 | 0.00 | 0.01 | 0.00 | 0.01 | |||||||||
| 7 (2 chains) | 4.20 | 0.01 | 0.00 | 0.02 | 0.03 | 0.06 | 0.04 | 0.01 | 0.00 | |||||||||
| 5 (2 chains) | 0.03 | 0.05 | 0.01 | 0.08 | 0.70 | 0.77 | 0.05 | 0.08 | 0.01 | |||||||||
| 2 (2 chains) | 7.00 | 0.00 | 0.10 | 0.01 | 0.01 | 0.01 | 0.01 | 0.05 | 0.00 | |||||||||
| 2 (single chain) | 0.43 | 0.05 | 0.04 | 0.01 | 0.01 | 0.04 | 0.01 | 0.01 | 0.01 | |||||||||
| Tail vein | 8 (2 chains) | 42.20 | 0.01 | 0.01 | 0.01 | 0.06 | 0.03 | 0.03 | 0.01 | 0.00 | ||||||||
| 8 (single chain) | 2.70 | 0.00 | 0.00 | 0.01 | 0.01 | 0.01 | 0.02 | 0.01 | 0.17 | |||||||||
| 2 (single chain) | 0.09 | 0.01 | 0.05 | 0.01 | 0.01 | 0.01 | 0.04 | 0.01 | NA | |||||||||
| 3 × 1010 gc/vector/mouse | ||||||||||||||||||
| Portal vein | 8 (2 chains) | 3.97 | 0.00 | 0.00 | 0.01 | 0.02 | 0.01 | 0.00 | 0.00 | 0.00 | ||||||||
| 8 (single chain) | 0.60 | 0.00 | 0.00 | 0.02 | 0.03 | 0.00 | 0.00 | 0.00 | 0.02 | |||||||||
| 7 (2 chains) | 0.51 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.01 | 0.00 | 0.02 | |||||||||
| 5 (2 chains) | 0.77 | 0.02 | 0.04 | 0.20 | 0.20 | 0.60 | 0.04 | 1.40 | 0.07 | |||||||||
| 2 (2 chains) | 3.80 | 0.01 | 0.01 | 0.17 | 0.01 | 0.41 | 0.02 | 0.01 | 0.15 | |||||||||
| 2 (single chain) | 0.03 | 0.02 | 0.00 | 0.01 | 0.01 | 0.00 | 0.00 | 0.04 | 0.02 | |||||||||
| 1 × 1010 gc/vector/mouse | ||||||||||||||||||
| Portal vein | 8 (2 chains) | 0.47 | 0.00 | 0.01 | 0.03 | 0.01 | 0.00 | 0.01 | 0.00 | 0.00 | ||||||||
| 8 (single chain) | 0.06 | 0.00 | 0.00 | 0.00 | 0.05 | 0.00 | 0.00 | 0.00 | 0.00 | |||||||||
| 7 (2 chains) | 4.74 | 0.00 | 0.02 | 0.01 | 0.01 | 0.00 | 0.00 | 0.00 | 0.00 | |||||||||
| 5 (2 chains) | 0.57 | 0.02 | 0.02 | 0.06 | 0.10 | 0.22 | 0.01 | NA | 0.02 | |||||||||
| 2 (2 chains) | 0.01 | 0.05 | 0.00 | 0.05 | 0.03 | 0.04 | 0.01 | 0.19 | 0.01 | |||||||||
| 2 (single chain) | 0.00 | 0.00 | 0.00 | 0.17 | 0.00 | 0.00 | 0.00 | 0.02 | 0.04 | |||||||||
Dose and route of administration . | . | Tissue biodistribution, copies/cell . | . | . | . | . | . | . | . | . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | AAV serotype . | Liver . | Spleen . | Stomach . | Ileum . | Heart . | Lung . | Kidney . | Muscle . | Gonads . | ||||||||
| 1 × 1011 gc/vector/mouse | ||||||||||||||||||
| Portal vein | 8 (2 chains) | 9.60 | 0.01 | 0.02 | 0.00 | 0.26 | 0.01 | 0.07 | NA | 0.64 | ||||||||
| 8 (single chain) | 5.70 | 0.01 | 0.00 | 0.00 | 0.01 | 0.00 | 0.01 | 0.00 | 0.01 | |||||||||
| 7 (2 chains) | 4.20 | 0.01 | 0.00 | 0.02 | 0.03 | 0.06 | 0.04 | 0.01 | 0.00 | |||||||||
| 5 (2 chains) | 0.03 | 0.05 | 0.01 | 0.08 | 0.70 | 0.77 | 0.05 | 0.08 | 0.01 | |||||||||
| 2 (2 chains) | 7.00 | 0.00 | 0.10 | 0.01 | 0.01 | 0.01 | 0.01 | 0.05 | 0.00 | |||||||||
| 2 (single chain) | 0.43 | 0.05 | 0.04 | 0.01 | 0.01 | 0.04 | 0.01 | 0.01 | 0.01 | |||||||||
| Tail vein | 8 (2 chains) | 42.20 | 0.01 | 0.01 | 0.01 | 0.06 | 0.03 | 0.03 | 0.01 | 0.00 | ||||||||
| 8 (single chain) | 2.70 | 0.00 | 0.00 | 0.01 | 0.01 | 0.01 | 0.02 | 0.01 | 0.17 | |||||||||
| 2 (single chain) | 0.09 | 0.01 | 0.05 | 0.01 | 0.01 | 0.01 | 0.04 | 0.01 | NA | |||||||||
| 3 × 1010 gc/vector/mouse | ||||||||||||||||||
| Portal vein | 8 (2 chains) | 3.97 | 0.00 | 0.00 | 0.01 | 0.02 | 0.01 | 0.00 | 0.00 | 0.00 | ||||||||
| 8 (single chain) | 0.60 | 0.00 | 0.00 | 0.02 | 0.03 | 0.00 | 0.00 | 0.00 | 0.02 | |||||||||
| 7 (2 chains) | 0.51 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.01 | 0.00 | 0.02 | |||||||||
| 5 (2 chains) | 0.77 | 0.02 | 0.04 | 0.20 | 0.20 | 0.60 | 0.04 | 1.40 | 0.07 | |||||||||
| 2 (2 chains) | 3.80 | 0.01 | 0.01 | 0.17 | 0.01 | 0.41 | 0.02 | 0.01 | 0.15 | |||||||||
| 2 (single chain) | 0.03 | 0.02 | 0.00 | 0.01 | 0.01 | 0.00 | 0.00 | 0.04 | 0.02 | |||||||||
| 1 × 1010 gc/vector/mouse | ||||||||||||||||||
| Portal vein | 8 (2 chains) | 0.47 | 0.00 | 0.01 | 0.03 | 0.01 | 0.00 | 0.01 | 0.00 | 0.00 | ||||||||
| 8 (single chain) | 0.06 | 0.00 | 0.00 | 0.00 | 0.05 | 0.00 | 0.00 | 0.00 | 0.00 | |||||||||
| 7 (2 chains) | 4.74 | 0.00 | 0.02 | 0.01 | 0.01 | 0.00 | 0.00 | 0.00 | 0.00 | |||||||||
| 5 (2 chains) | 0.57 | 0.02 | 0.02 | 0.06 | 0.10 | 0.22 | 0.01 | NA | 0.02 | |||||||||
| 2 (2 chains) | 0.01 | 0.05 | 0.00 | 0.05 | 0.03 | 0.04 | 0.01 | 0.19 | 0.01 | |||||||||
| 2 (single chain) | 0.00 | 0.00 | 0.00 | 0.17 | 0.00 | 0.00 | 0.00 | 0.02 | 0.04 | |||||||||
A single mouse for each serotype per dose and injection route was humanely killed at 4 months after vector administration. gDNA was extracted from 9 different tissues for TaqMan DNA PCR. The primers and probes were targeted to the SV40 poly A region.
NA indicates not assessed.