RNAI AGENTS, COMPOSITIONS AND METHODS FOR USE THEREOF FOR TREATING TRANSTHYRETIN (TTR) ASSOCIATED DISEASES Russian patent published in 2019 - IPC C07H21/00 C12N15/113 A61K31/7088 A61K31/713 

FIELD: biochemistry.

SUBSTANCE: described is a double-stranded RNAi agent for inhibiting the expression of transthyretin (TTR), containing the sense strand complementary to the anti-sense strand, where the specified anti-sense strand contains a sequence complementary to nucleotides 504–526 of the gene of transthyretin (TTR) (SEQ ID NO:1), where the sense strand has a length of 21 nucleotides, and the anti-sense strand has a length of 23 nucleotides. Described is the RNAi agent for inhibiting transthyretin expression (TTR), including the sense strand and the anti-sense strand, in which the sense strand contains the nucleotide sequence 5’-UfgGfgAfuUfuCfAfUfgUfaacCfaAfgAfL96-3’ (SEQ ID NO:2), and the anti-sense strand contains the nucleotide sequence 5’-uCfuUfgGfUfUfaCfaugAfaAfuCfcCfasUfsc-3’ (SEQ ID NO:3), where a, g, c and u represent 2'—O-methyl (2'-OMe) A, G, C and U; Af, Gf, Cf and Uf represent 2'-fluoro A, G, C and U; s represents a phosphorothioate bond; and L96 represents GalNAc₃ ligand. Described is a pharmaceutical composition containing any of these substances. Presented is a method for inhibiting the expression of transthyretin (TTR) in the cell, including bringing the specified cell into contact with the specified RNAi agent.

EFFECT: method for treating a disease associated with TTR in an individual is presented, comprising administering to said individual a therapeutically effective amount of said RNAi agent.

35 cl, 10 tbl, 11 ex