JP-2022510041-A5 -

Dates

Publication Date

20221209

Application Date

20191202

Description

Details of one or more embodiments are shown in the following description. Other features, purposes, and advantages will become apparent from the description and the claims. In certain embodiments, for example, the following are provided: (Item 1) An oligonucleotide comprising a single-stranded oligonucleotide with a length of 10 to 30 linked nucleosides, comprising a region of at least 10 consecutive nucleic acid bases having at least 80% complementarity to the MSH3 gene. (Item 2) The oligonucleotide is (a) DNA core sequence containing linked deoxyribonucleosides; (b) 5' adjacent sequences containing linked nucleosides; and (c) 3' adjacent sequence containing linked nucleosides Includes, The oligonucleotide according to item 1, wherein the DNA core comprises a region of at least 10 consecutive nucleic acid bases having at least 80% complementarity to the MSH3 gene, and is positioned between the 5' adjacency sequence and the 3' adjacency sequence; the 5' adjacency sequence and the 3' adjacency sequence each comprise at least two linked nucleosides; and at least one nucleoside in each adjacency sequence comprises an alternative nucleoside. (Item 3) An oligonucleotide comprising a single-stranded oligonucleotide with a length of 10 to 30 linked nucleosides for inhibiting the expression of the human MSH3 gene in cells, wherein the oligonucleotide comprises a region of at least 10 consecutive nucleic acid bases having at least 80% complementarity to the MSH3 gene. (Item 4) The oligonucleotide is (a) DNA core containing linked deoxyribonucleosides; (b) 5' adjacent sequences containing linked nucleosides; and (c) 3' adjacent sequence containing linked nucleosides Includes, The oligonucleotide according to item 3, wherein the DNA core comprises a region of at least 10 consecutive nucleic acid bases having at least 80% complementarity to the MSH3 gene, and is positioned between the 5' adjacency sequence and the 3' adjacency sequence; the 5' adjacency sequence and the 3' adjacency sequence each comprise at least two linked nucleosides; and at least one nucleoside of each adjacency sequence comprises an alternative nucleoside. (Item 5) The oligonucleotide according to any one of items 1 to 4, wherein the region of at least 10 nucleic acid bases has at least 90% complementarity with the MSH3 gene. (Item 6) The oligonucleotide according to any one of items 1 to 5, wherein the region of at least 10 nucleic acid bases has at least 95% complementarity with the MSH3 gene. (Item 7) The region of at least 10 nucleic acid bases corresponds to the MSH3 gene of the sequence of reference mRNA NM_002439.4, specifically the regions 155-199, 355-385, 398-496, 559-589, 676-724, 762-810, 876-903, 912-974, 984-1047, 1054-1098, 1114-1179, 1200-1227, 1294-1337, 1392-1417, 1467-1493, 1517-1630, 1665-1747, 1768-1866, 2029-2063, 2087-2199, 2262-2293, and 2304 of the MSH3 gene. An oligonucleotide according to any one of items 1 to 6, which is complementary at one or more positions among the following positions: ~2330, 2371~2410, 2432~2458, 2494~2521, 2539~2647, 2679~2713, 2727~2753, 2767~2920, 2933~3000, 3046~3073, 31323245, 3266~3306, 3397~3484, 3528~3575, 3591~3617, 3753~3792, 3901~3936, 4074~4101, or 4281~4319. (Item 8) The region of at least 10 nucleic acid bases corresponds to the MSH3 gene of the sequence of reference mRNA NM_002439.4, specifically to 155-199, 359-385, 398-496, 559-589, 676-724, 762-810, 876-974, 984-1098, 1114-1179, 1200-1227, 1294-1337, 1392-1417, 1467-1493, 1517-1630, 1665-1747, 1834-1866, 2029-2056, 2093-2199, 2262-2293, 2304-2329, and 237 An oligonucleotide according to any one of items 1 to 6, which is complementary at one or more positions among positions 1 to 2410, 2433 to 2458, 2494 to 2521, 2539 to 2647, 2679 to 2713, 2727 to 2753, 2767 to 2920, 2933 to 3000, 3046 to 3072, 3132 to 3245, 3266 to 3303, 3397 to 3484, 3528 to 3575, 3591 to 3617, 3753 to 3792, 3901 to 3936, 4076 to 4101, or 4281 to 4319. (Item 9) The region of at least 10 nucleic acid bases corresponds to the MSH3 gene of the sequence of reference mRNA NM_002439.4, specifically the regions 155-196, 359-385, 413-462, 559-589, 676-724, 762-810, 876-974, 984-1096, 1114-1179, 1200-1227, 1294-1337, 1467-1493, 1517-1630, 1665-1747, 1834-1866, 2029-2056, 2093-2199, 2265-2293, and 237 of the MSH3 gene. An oligonucleotide according to any one of items 1 to 6, which is complementary at one or more positions among positions 8-2410, 2433-2458, 2494-2521, 2539-2647, 2679-2712, 2727-2753, 2767-2919, 2934-3000, 3046-3071, 3144-3183, 3220-3245, 3397-3484, 3534-3575, 3591-3616, 3901-3931, or 4281-4306. (Item 10) The oligonucleotide according to any one of items 1 to 6, wherein the region of at least 10 nucleic acid bases is complementary to the MSH3 gene corresponding to the sequence of reference mRNA NM_002439.4 at one or more positions among 435-462, 559-584, 763-808, 876-902, 931-958, 1001-1083, 1114-1179, 1294-1337, 1544-1578, 1835-1863, 2031-2056, 2144-2169,