Quantification of AAV-cFVIII vectors in the liver following long-term follow-up in the hemophilia A dog model
| ID . | AAV dose vg/kg . | Treatment age (y) . | Follow-up (y) . | CSA FVIII:C (%) . | N . | TES . | LAM-PCR . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TES seq . | Total IS seq . | TES unique IS . | Int VCN vg/cell . | LAM-PCR seq . | LAM-PCR unique IS . | LAM-PCR IS per cell . | ||||||
| ALX | AAV6 1.0e13 | 0.7 | 10.5 | 8.6% | 1 2 | 2324084 3525725 | 293 688 | 239 434 | 6.18e−4 1.12e−3 | 87797 n/a | 360 n/a | 6.20e−4 n/a |
| ANG∗ | AAV2 1.5e13 | 1.0 | 11.5 | 0.5% | 1 2 | 2264496 3016959 | 1363 1377 | 310 58 | 8.01e−4 1.50e−4 | 284365 n/a | 167 n/a | 2.88e−4 n/a |
| ELI | AAV2 6.0e12 | 0.6 | 8.2 | † | 1 2 | 2915252 2406745 | 385 656 | 269 496 | 6.95e−4 1.28e−3 | 257439 n/a | 213 n/a | 3.67e−4 n/a |
| FLO | AAV8 1.0e13 | 1.0 | 10.5 | 1.8% | 1 2 | 3057875 3237835 | 838 887 | 362 413 | 9.35e−4 1.07e−3 | n/a n/a | n/a n/a | n/a n/a |
| JUN | AAV2 2.7e13 | 1.0 | 12.0 | 7.2% | 1 2 | 2286381 2494473 | 948 700 | 550 534 | 1.42e−3 1.38e−3 | 160937 n/a | 380 n/a | 6.55e−4 n/a |
| MG∗ | AAV6 1.7e13 | 0.5 | 11.5 | 0.3% | 1 2 | 2597851 2525320 | 436 152 | 49 105 | 1.27e−4 2.71e−4 | 146726 n/a | 67 n/a | 1.15e−4 n/a |
| MZ | AAV6 1.0e13 | 1.3 | 10.1 | 7.9% | 1 2 | 2369218 2355983 | 650 458 | 243 353 | 6.28e−4 9.12e−4 | n/a n/a | n/a n/a | n/a n/a |
| VC | AAV2 1.5e13 | 0.7 | 11.0 | 2.9% | 1 2 | 3855884 2012102 | 1349 353 | 1055 276 | 2.73e−3 7.13e−4 | n/a 228238 | n/a 196 | n/a 3.38e−4 |
| TB | Control | n/a | n/a | n/a | 1 | 2805661 | 4 | 4 | 1.03e−5 | n/a | n/a | n/a |
| ID . | AAV dose vg/kg . | Treatment age (y) . | Follow-up (y) . | CSA FVIII:C (%) . | N . | TES . | LAM-PCR . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TES seq . | Total IS seq . | TES unique IS . | Int VCN vg/cell . | LAM-PCR seq . | LAM-PCR unique IS . | LAM-PCR IS per cell . | ||||||
| ALX | AAV6 1.0e13 | 0.7 | 10.5 | 8.6% | 1 2 | 2324084 3525725 | 293 688 | 239 434 | 6.18e−4 1.12e−3 | 87797 n/a | 360 n/a | 6.20e−4 n/a |
| ANG∗ | AAV2 1.5e13 | 1.0 | 11.5 | 0.5% | 1 2 | 2264496 3016959 | 1363 1377 | 310 58 | 8.01e−4 1.50e−4 | 284365 n/a | 167 n/a | 2.88e−4 n/a |
| ELI | AAV2 6.0e12 | 0.6 | 8.2 | † | 1 2 | 2915252 2406745 | 385 656 | 269 496 | 6.95e−4 1.28e−3 | 257439 n/a | 213 n/a | 3.67e−4 n/a |
| FLO | AAV8 1.0e13 | 1.0 | 10.5 | 1.8% | 1 2 | 3057875 3237835 | 838 887 | 362 413 | 9.35e−4 1.07e−3 | n/a n/a | n/a n/a | n/a n/a |
| JUN | AAV2 2.7e13 | 1.0 | 12.0 | 7.2% | 1 2 | 2286381 2494473 | 948 700 | 550 534 | 1.42e−3 1.38e−3 | 160937 n/a | 380 n/a | 6.55e−4 n/a |
| MG∗ | AAV6 1.7e13 | 0.5 | 11.5 | 0.3% | 1 2 | 2597851 2525320 | 436 152 | 49 105 | 1.27e−4 2.71e−4 | 146726 n/a | 67 n/a | 1.15e−4 n/a |
| MZ | AAV6 1.0e13 | 1.3 | 10.1 | 7.9% | 1 2 | 2369218 2355983 | 650 458 | 243 353 | 6.28e−4 9.12e−4 | n/a n/a | n/a n/a | n/a n/a |
| VC | AAV2 1.5e13 | 0.7 | 11.0 | 2.9% | 1 2 | 3855884 2012102 | 1349 353 | 1055 276 | 2.73e−3 7.13e−4 | n/a 228238 | n/a 196 | n/a 3.38e−4 |
| TB | Control | n/a | n/a | n/a | 1 | 2805661 | 4 | 4 | 1.03e−5 | n/a | n/a | n/a |
Control, untreated hemophilia A control dog; CSA, chromogenic substrate FVIII activity assay, using a pooled normal canine standard (12-20 normal dogs); Epi VCN, episomal vector copy number; Int VCN, integrated vector copy number; N, liver sample number (ie, ALX sample 1 = ALX-1); n/a, not available; Seq, sequencing reads.
Nonresponder
Terminal sample not available: earlier CSA FVIII:C on-study: 3.4% to 5.7%.