3ANGPTL3 iRNA ANGIOPOIETIN-LIKE 3ANGPTL3 IRNA COMPOSTIONS AND METHODS OF USE THEREOF

• Main Authors: BETTENCOURT BRIAN, MILSTEIN STUART, FRANK KAMENETSKY MARIA, FITZGERALD KEVIN, QUERBES WILLIAM, SHULGA MORSKAYA SVETLANA
• Format: Patent
• Language: English; Korean
• Published: 31.03.2021
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

본 발명은 ANGPL3 유전자의 RNA 전사물의 RNA-유발성 침묵화 복합체(RISC)-매개 절단이 발생하도록 하는 iRNA 조성물을 제공한다. ANGPL3 유전자는 세포, 예컨대, 인간과 같은 피검자 내의 세포 내에 있을 수 있다. 또한, 본 발명은 ANGPL3 유전자의 발현을 억제하고/하거나, ANGPL3 유전자의 발현의 억제 또는 감소로 이득을 보게 되는 피검자, 예컨대, 고지질혈증 또는 고중성지방혈증을 앓고 있거나 앓기 쉬운 피검자와 같이, 지질 대사 질환을 앓고 있거나 앓기 쉬운 피검자를 치료하기 위한 본 발명의 iRNA 조성물의 사용 방법을 제공한다. The invention relates to a double-stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Angiopoietin-like 3 (ANGPTL3), comprising a sense strand and an antisense strand forming a duplex region, wherein the sense strand comprises at least 15, preferably at least 16 and most preferably at least 17 contiguous nucleotides of the nucleotide sequence 5'-GUCUCAAAAUGGAAGGUUAUA-3' (SEQ ID NO: 1160), wherein the antisense strand comprises at least 15 contiguous nucleotides of the nucleotide sequence 5'-UAUAACCUUCCAUUUUGAGACUU-3' (SEQ ID NO: 1341), wherein at least one of the modified nucleotides is selected from the group consisting of a 2'-O-methyl modified nucleotide, a 2'-fluoro modified nucleotide, and a nucleotide comprising a 5'-phosphorothioate group, and wherein a ligand comprising an N-acetylgalactosamine (GaINAc) is conjugated to at least one strand of the dsRNA agent.