RNAi AGENTS COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATING TRANSTHYRETIN TTR ASSOCIATED DISEASES

본 발명은 트랜스티레틴(TTR) 유전자를 타겟으로 하는 RNAi 제제, 예를 들면, 이중가닥 RNAi 제제들, 및 TTR-관련 질병들을 치료 또는 예방하기 위해 상기 RNAi 제제들을 사용하는 방법을 제공한다. The present invention relates to a double stranded RNAi agent comprising a sense strand complementary to an antisense strand, wherein said antisense strand comprises a region substantially complementary to nucleotides 504 to 526 of the transthyretin (TTR) gene of SEQ ID NO: 1, wherein the sense strand is 21 nucleotides in length and the antisense strand is 23 nucleotides in length, wherein said double stranded RNAi agent comprises the sense strand represented by the following formula (I): 5' np -Na -(X X X)i-Nb -Y Y Y -Nb -(Z Z Z)j -Na - nq 3' (I) wherein: i is 1 and j is 0; or i is 0 and j is 1; or both i and j are each independently 0 or 1; p and q are each independently 0-6; each Na independently represents an oligonucleotide sequence comprising 0-25 modified nucleotides, each sequence comprising at least two differently modified nucleotides; each Nb independently represents an oligonucleotide sequence comprising 0-10 modified nucleotides; each np and nq independently represents an overhang nucleotide; XXX, YYY and ZZZ each independently represent one motif of three identical modifications on three consecutive nucleotides; modifications on Nb differ from the modification on Y; wherein YYY is all 2'-F modified nucleotides; and wherein the sense strand is conjugated to at least one ligand, wherein the ligand is a Ga1NAc ligand at 3' end.