Nucleic acids for inhibiting expression of tmprss6 and iron chelators
AssigneeSilence Therapeutics GmbH
InventorUte Schaeper
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Abstract
The present invention relates to products and compositions and their uses. In particular the invention relates to nucleic acid products that interfere with the TMPRSS6 gene expression or inhibits its expression in combination with one or more iron chelators and possibly other active agents, as well as therapeutic uses such as for the treatment of hemochromatosis, porphyria and blood disorders such as beta-thalassemia, sickle cell disease and transfusional iron overload or myelodysplastic syndrome, and infections and non-relapse related mortality associated with bone marrow transplantation.
Claims17
-17. (canceled)
A method of treating a disease or disorder comprising administration of a combination comprising a nucleic acid for inhibiting expression of TMPRSS6 and one or more iron chelators to an individual in need of treatment thereof,
- wherein the nucleic acid comprises at least one duplex region that comprises at least a portion of a first strand and at least a portion of a second strand that is at least partially complementary to the first strand, wherein said first strand is at least partially complementary to at least a portion of RNA transcribed from the TMPRSS6 gene, wherein said first strand comprises a nucleotide sequence selected from the following sequences:
- SEQ ID NOs:
- 333, 317, 319, 321, 323, 325, 327, 329, 331, 335, 337, 339, 341, 343, 345, 353, 356, 358, 360, 362, 364, 366, 368, 370, 372, 374, 376, 378, 380, 382, 384, 386, 388, 390, 392, 394, 396, 398, 400, 402, 404, 406, 407, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, or 442.
A method of treating a disease or disorder comprising administration of a combination comprising a nucleic acid for inhibiting expression of TMPRSS6 and one or more iron chelators to an individual in need of treatment thereof, wherein the nucleic acid comprises at least one duplex region that comprises at least a portion of a first strand and at least a portion of a second strand that is at least partially complementary to the first strand, wherein said first strand is at least partially complementary to at least a portion of RNA transcribed from the TMPRSS6 gene, wherein the first strand comprises the nucleotide sequence of SEQ ID NO:17 and the second strand comprises the nucleotide sequence of SEQ ID NO:18.
A method of treating a disease or disorder comprising administration of a combination comprising a nucleic acid for inhibiting expression of TMPRSS6 and one or more iron chelators to an individual in need of treatment thereof, wherein the nucleic acid comprises at least one duplex region that comprises at least a portion of a first strand and at least a portion of a second strand that is at least partially complementary to the first strand, wherein said first strand is at least partially complementary to at least a portion of RNA transcribed from the TMPRSS6 gene, and wherein said first strand comprises the nucleotide sequence 5′ aaccagaagaagcagguga 3′ (SEQ ID NO:17) comprising modifications 6273646282647284546, and wherein said second strand comprises the nucleotide sequence 5′ ucaccugcuucuucugguu 3′ (SEQ ID NO:18) comprising modifications 1727354715351718451,
- wherein the specific modifications are depicted by the following numbers
- 1=2′F-dU;
- 2=2′F-dA;
- 3=2′F-dC;
- 4=2′F-dG;
- 5=2′-OMe-rU;
- 6=2′-OMe-rA;
- 7=2′-OMe-rC;
- and
- 8=2′-OMe-rG.
Dependencies are inferred from the claim text.