Table 1.
| No. | Abbr. Name |
Sequence | Position of Mismatch |
Tm, °C | mut IC50 (nM) |
wt IC50 (nM) | Selectivity (fold) |
|---|---|---|---|---|---|---|---|
| ssRNAs with 5’-(E)-vinyl phosphonate chemistry: | |||||||
| 537787 | REP |  |
None | 90–91 | 8.0 ± 1.7 | > 100 | >13 |
| 537775 | P9 |  |
9 | 84–85 | 3.5 ± 0.3 | > 100 | >29 |
| 537786 | P10 |  |
10 | 84–85 | 22.3 ± 2.6 | > 100 | >4 |
| ssRNAs with 5’-phosphate chemistry: | |||||||
| 553819 | REP |  |
None | > 95 | 5.7 ± 1.4 | 71.8 ± 15.6 | 13 |
| 556886 | P4 |  |
4 | 85 | 8.8 | 61.1 | 7 |
| 556887 | P5 |  |
5 | 82–89 | 17.2 ± 2.6 | >100 | >6 |
| 556888 | P6 |  |
6 | 81–85 | N.I. | N.I. | N/A |
| 556889 | P7 |  |
7 | 83–85 | 11.2 ± 1.7 | 51.1 ± 8.5 | 5 |
| 556890 | P8 |  |
8 | 83–85 | 4.1 ± 0.7 | 29.5 ± 4.3 | 7 |
| 553822 | P9 |  |
9 | 85 | 4.9 ± 0.8 | 90.4 ± 9.7 | 18 |
| 553821 | P10 |  |
10 | 82–86 | 17.8 ± 3.5 | >100 | >6 |
| 557407 | P10R |  |
10 | 77–80 | 15.3 ± 2.4 | >100 | >7 |
| 556891 | P11 |  |
11 | 78–81 | 12.8 ± 1.7 | >100 | >8 |
| 556892 | P12 |  |
12 | 81–84 | 3.4 ± 0.6 | 72.0 ± 12.3 | 21 |
| 557406 | P13 |  |
13 | 78–82 | 4.2 ± 0.6 | >100 | >24 |
| 557408 | P16 |  |
16 | 81–84 | 8.1 | 27.3 | 3 |
| 557409 | P910 |  |
9, 10 | 78–81 | 6.3 ± 0.5 | >100 | >16 |
| 557426 | PM3 |  |
9, 10, 11 | 74 | 3.3 ± 0.5 | >100 | >30 |
| 557427 | PM4 |  |
8, 9, 10, 11 | 65–66 | 11.8 ± 1.9 | >100 | >8 |
| 557428 | RM3 |  |
4, 10, 16 | 65 | 22.3 | >100 | >4 |
| 557429 | RM4 |  |
3, 8, 13, 17 | 65–66 | N.I. | N.I. | N/A |
| 557430 | REPU |  |
None | >95 | 19.4 ± 4.7 | >100 | >5 |
| Control oligomers: | |||||||
| 388916 | Gapmer |  |
N/A | N/A | 7.4 ± 0.7 | 12.6 ± 1.3 | 1.7 |
| 387898 | Gapmer |  |
N/A | N/A | 5.8 | 7.1 | 1.2 |
| 522247 | Neg.Ctrl |  |
N/A | N/A | N.I. | N.I. | N/A |
| N/A | LNAT |  |
None | 97 | 40 ± 7 | >100 | >2.5 |
| N/A | CM |
5’-GCUAUACCAGCGUCGUCAUAA-3’ 3’-TTCGA UAUGGUCGCAGCAGUA-5’ |
N/A | N/A | N.I. | N.I. | N/A |
Color schemes represent different chemical modifications as follows:
All other sugars are riboses unless specifiied otherwise.
N.I.: no inhibition; N/A: not available.
Except for CM (a dsRNA species), all Tm’s are measured using ss-siRNAs duplexed with equi-molar of unmodified ssRNA of the sequence 5’-CAGCAGCAGCAGCAGCAGCAGC-3’.
Gapmers are entirely of phosphorothioate backbone, with 10 central bases having deoxy-ribose and each 5 flanking bases being 2’-MOE chemistry.
All data were obtained in HD-patient-derived fibroblast GM 04281 cell-line. Selectivity is calculated by dividing IC50 of wild-type HTT by that of mutant HTT. Error ranges represent standard error of the mean (SEM) of IC50 values from biological replicates or multiplicates.