公开(公告)号：WO2023081847A1

公开(公告)日：2023-05-11

申请号：PCT/US2022/079336

申请日：2022-11-04

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： STITT, Trevor ,  BRYDGES, Susannah ,  MUJICA, Alexander O. ,  ALLY, Roxanne

IPC: A01K67/027 ,  C07K14/47

Abstract: Non-human animal cells and non-human animals comprising a humanized Cacng1 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized Cacng1 locus express a human CACNG1 protein or fragments thereof.

公开(公告)号：WO2018064600A1

公开(公告)日：2018-04-05

申请号：PCT/US2017/054551

申请日：2017-09-29

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： HESLIN, David ,  ALLY, Roxanne ,  SIAO, Chia-Jen ,  LAI, Ka-Man, Venus ,  VALENZUELA, David, M. ,  GUO, Chunguang ,  LACROIX-FRALISH, Michael ,  MACDONALD, Lynn ,  SHARMA, Aarti ,  KAJIMURA, Daisuke ,  DROGUETT, Gustavo ,  FRENDEWEY, David

IPC: A01K67/027 ,  C12N15/90 ,  C12N15/113

Abstract: A non-human animal (e.g., a rodent) model for diseases associated with a C9ORF72 heterologous hexanucleotide repeat expansion sequence is provided, which non-human animal comprises a heterologous hexanucleotide repeat (GGGGCC) in an endogenous C9ORF72 locus. A non-human animal disclosed herein comprising a heterologous hexanucleotide repeat expansion sequence comprising at least one instance, e.g., repeat, of a hexanucleotide (GGGGCC) sequence may further exhibit a characteristic and/or phenotype associated with one or more neurodegenerative disorders (e.g., amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD), etc.). Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)) are also provided.

Abstract translation: 提供了与C9ORF72异源六核苷酸重复扩增序列相关的疾病的非人动物（例如啮齿动物）模型，所述非人动物包含异源六聚核苷酸 在内源性C9ORF72基因座中重复（GGGGCC）。 本文公开的包含包含六核苷酸（GGGGCC）序列的至少一个实例，例如重复序列的异源六核苷酸重复扩增序列的非人动物还可以表现出与一种或多种神经变性病症（例如， 肌萎缩侧索硬化（ALS）和/或额颞叶痴呆（FTD）等）。 还提供了可用于预防，延缓或治疗一种或多种神经变性（例如，肌萎缩侧索硬化（ALS，也称为Lou Gehrig病）和额颞痴呆（FTD））的治疗候选物的方法。