公开(公告)号：WO2021119226A1

公开(公告)日：2021-06-17

申请号：PCT/US2020/064159

申请日：2020-12-10

Applicant: ALNYLAM PHARMACEUTICALS, INC. ,  REGENERON PHARMACEUTICALS, INC.

Inventor： FISHILEVICH, Elane ,  MILSTEIN, Stuart ,  BROWN, Kirk ,  ZIMMERMANN, Tracy ,  MCININCH, James, D. ,  FRENDEWEY, David ,  CHIAO, Eric ,  SHARMA-KANNING, Aarti ,  GAGLIARDI, Anthony ,  DROGUETT, Gustavo ,  DUBOSE, Brittany ,  ZAMBROWICZ, Brian

IPC: C12N15/113 ,  A61K31/713 ,  A61P25/28

Abstract: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a human chromosome 9 open reading frame 72 (C9orf72) gene, as well as methods of inhibiting expression of a C9orf72 gene and methods of treating subjects having a C9orf72-associated disease or disorder, e.g., C9orf72 amyotrophic lateral sclerosis/frontotemporal dementia or Huntington-Like Syndrome Due To C9orf72 Expansions, using such dsRNAi agents and compositions.

公开(公告)号：WO2020131632A1

公开(公告)日：2020-06-25

申请号：PCT/US2019/066317

申请日：2019-12-13

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： KAJIMURA, Daisuke ,  SHARMA-KANNING, Aarti ,  DUBOSE, Brittany ,  DROGUETT, Gustavo ,  SIAO, Chia-Jen ,  KUNO, Junko ,  FRENDEWEY, David ,  ZAMBROWICZ, Brian

IPC: C12N15/10 ,  A01K67/027 ,  C12N15/11

Abstract: Nuclease-mediated methods for expanding repeats already present at a genomic locus are provided. Non-human animal genomes, non-human animal cells, and non-human animals comprising a heterologous hexanucleotide repeat expansion sequence inserted at an endogenous C9orf72 locus and methods of making such non-human animal cells and non-human animals through nuclease-mediated repeat expansion are also provided. Methods of using the non-human animal cells or non-human animals to identify therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative disorders associated with repeat expansion at the C9orf72 locus are also provided.