Table 1.
Biodistribution of H10 mRNA in Plasma and Tissue after IM Administration in Mice
| Matrix | tmax (hr) | Cmax (ng/mL) |
AUC0–264 h (ng.hr/mL) |
t1/2 (h) | ||
|---|---|---|---|---|---|---|
| Mean | SE | Mean | SE | |||
| Bone marrow | 2.0 | 3.35 | 1.87 | NA | NC | |
| Brain | 8.0 | 0.429 | 0.0447 | 13.9 | 1.61 | NR |
| Cecum | 8.0 | 0.886 | 0.464 | 11.1 | 5.120 | NC |
| Colon | 8.0 | 1.11 | 0.501 | 13.5 | 5.51 | NC |
| Distal lymph nodes | 8.0 | 177.0 | 170.0 | 4,050 | 2,060 | 28.0 |
| Heart | 2.0 | 0.799 | 0.225 | 6.76 | 1.98 | 3.50 |
| Ileum | 2.0 | 3.54 | 2.60 | 22.6 | 10.8 | 5.42 |
| Jejunum | 2.0 | 0.330 | 0.120 | 5.24 | 0.931 | 8.24 |
| Kidney | 2.0 | 1.31 | 0.273 | 9.72 | 1.44 | 11.4 |
| Liver | 2.0 | 47.2 | 8.56 | 276 | 37.4 | NC |
| Lung | 2.0 | 1.82 | 0.555 | 12.7 | 2.92 | 16.0 |
| Muscle (injection site) | 2.0 | 5,680 | 2,870 | 95,100 | 20,000 | 18.8 |
| Plasma | 2.0 | 5.47 | 0.829 | 35.5 | 5.41 | 9.67 |
| Proximal lymph nodes | 8.0 | 2,120 | 1,970 | 38,600 | 22,000 | 25.4 |
| Rectum | 2.0 | 1.03 | 0.423 | 14.7 | 3.67 | NR |
| Spleen | 2.0 | 86.9 | 29.1 | 2,270 | 585 | 25.4 |
| Stomach | 2.0 | 0.626 | 0.121 | 11.6 | 1.32 | 12.7 |
| Testes | 8.0 | 2.37 | 1.03 | 36.6 | 11.8 | NR |
Male CD-1 mice received 300 μg/kg (6 μg) formulated H10 mRNA via IM immunization. Two replicates of bone marrow, lung, liver, heart, right kidney, inguinal- and popliteal-draining lymph nodes, axillary distal lymph nodes, spleen, brain, stomach, ileum, jejunum, cecum, colon, rectum, testes (bilateral), and injection site muscle were collected for bDNA analysis at 0, 2, 8, 24, 48, 72, 120, 168, and 264 hr after dosing (n = 3 mice/time point). NA, not applicable AUC with less than three quantifiable concentrations; NC, not calculated; NR, not reported because extrapolation exceeds 20% or R-squared is less than 0.80.