Table 1.
Structures and Key Data of Initial Set of Tool LNA-ASOs
| LNA-ASO Name | LNA-ASO Sequence | Target RNA | Target Species | ALT Increase Relative to Control | Hepatotoxic | Tm (°C) |
|---|---|---|---|---|---|---|
| LNA32 | EAAaggaaacacaEAT | Myd88 | mouse, rat | 1.09 | no | 44.5 |
| LNA33 | EAAatgctgaaacTAT | Myd88 | mouse | 1.02 | no | 44.0 |
| LNA39 | GTEagaaacaaccAEE | Myd88 | mouse, rat | 1.06 | no | 51.4 |
| LNA41 | EAEattccttgctETG | Myd88 | mouse, human | 44.57 | yes | 57.2 |
| LNA37 | GEEtcccagttccTTT | Myd88 | mouse, rat | 41.54 | yes | 64.3 |
| LNA43 | GATgcctcccaGTT | Myd88 | mouse, rat | 36.48 | yes | 55.9 |
Capital letters: LNA; small letters: DNA; E, 5-methylcytosin; all LNA-ASOs were fully phosphorothioated. The LNA-ASOs were designed to target Myd88, with some also targeting rat Myd88 or human MYD88, as indicated. ALT levels were determined 2 weeks after i.v. treatment of mice with 5 × 15 mg/kg.6 ALT levels are expressed as fold change relative to saline-treated animals. The theoretically calculated melting temperatures (Tms) are indicated.