Table 1.
Summary of VGC and fold human FXN transgene mRNA expression over endogenous mouse Fxn mRNA expression as measured by ddPCR. Data are shown as mean ± SD.
| Mouse | MCK-Fxn | WT | WT | |||||
|---|---|---|---|---|---|---|---|---|
| Transgene | FXNWT | FXNWT | FXNN146K | FXNWT | FXNN146K | |||
| Dose (vg/kg) | 1E13 | 3E13 | 1E14 | 3E13 | 1E13 | |||
| Time at euthanasia | ||||||||
| dpi | 57 | 26–57 | 20-26 | 21 | 21 | 35 | 56 | 56 |
| wpi | 8 | 3.7–8 | 2.8–3.7 | 3 | 3 | 5 | 8 | 8 |
| Vector genome copy number (vg/μg gDNA) | ||||||||
| Heart | 2.4 ± 1.3E+04 | 1.2 ± 1.4E+05 | 4.4 ± 1.8E+05 | 1.1 ± 0.3E+05 | 1.1 ± 0.7E+05 | nd | 1.2 ± 0.6E+04 | 8.8 ± 3.5E+03 |
| Liver | 5.7 ± 2.6E+05 | 6.5 ± 1.4E+06b | 2.0 ± 0.4E+07 | 7.3 ± 1.8E+06 | 7.8 ± 5.0E+06 | 4.0 ± 1.4E+05 | 5.0 ± 2.2E+04 | 1.2 ± 0.3E+06 |
| Fold FXN mRNA expression over mouse Fxn | ||||||||
| Heart | 51 ± 26a | 159 ± 57a | 735 ± 289a | 89 ± 25 | 44 ± 27 | nd | 8 ± 4 | 10 ± 5 |
| Liver | 57 ± 27 | 489 ± 209b | 776 ± 292 | 930 ± 325 | 568 ± 132 | 109 ± 26 | 14 ± 16 | 215 ± 57 |
dpi: days post-injection; wpi: weeks post-injection; nd: not determined.
a
Fold change was determined using the mean value of mouse Fxn expression as measured in WT untreated group.
b
Only animals euthanized between 26 and 30 dpi were used due to loss of transgene expression in liver of animals euthanized at later time points.