公开(公告)号：US20240409890A1

公开(公告)日：2024-12-12

申请号：US18739113

申请日：2024-06-10

Applicant: Li Gan et al. ,  Shiaoching Gong ,  Celeste Parra Bravo ,  Zeping Zhao

Inventor： Li Gan et al. ,  Shiaoching Gong ,  Celeste Parra Bravo ,  Zeping Zhao

IPC: C12N5/0793 ,  A61K31/343 ,  A61P25/28 ,  C07K14/47 ,  C12N5/00 ,  C12N9/22 ,  C12N15/113 ,  G01N33/50

Abstract: Provided herein are iPSC lines engineered to express 4R-tau and 4R-tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes, including shared transcriptomic signatures, autophagic body accumulation, and impaired neuronal activity. A CRISPRi screening of genes associated with Tau pathobiology identified over 500 genetic modifiers of Tau-seeding-induced Tau propagation, including retromer VPS29 and the UFMylation cascade as top modifiers. In AD brains, the UFMylation cascade is altered in neurofibrillary-tangle-bearing neurons. Inhibiting the UFMylation cascade suppressed seeding-induced Tau propagation. Also provided herein is a platform to identify novel therapeutic strategies for 4R tauopathy.

公开(公告)号：US20050210539A1

公开(公告)日：2005-09-22

申请号：US10995066

申请日：2004-11-22

Applicant: Nathaniel Heintz ,  Peter Model ,  Xiangdong Yang ,  Shiaoching Gong

Inventor： Nathaniel Heintz ,  Peter Model ,  Xiangdong Yang ,  Shiaoching Gong

IPC: A01K67/027 ,  C07K14/47 ,  C12N15/09 ,  C12N15/10 ,  C12N15/64 ,  C12N15/65 ,  C12N15/70 ,  C12N15/85 ,  C12N15/86 ,  C12N15/90

CPC classification number: A01K67/0275 ,  A01K67/0276 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0356 ,  C07K14/4705 ,  C12N15/102 ,  C12N15/64 ,  C12N15/65 ,  C12N15/70 ,  C12N15/8509 ,  C12N15/902 ,  C12N2800/204 ,  C12N2800/30 ,  C12N2840/203 ,  C12N2840/206

Abstract: A simple method for modifying genes in a recombination deficient host cell is disclosed. Such modifications include generating insertions, deletions, substitutions, and/or point mutations at any chosen site in the independent origin based cloning vector. The modified gene is contained in an independent origin based cloning vector that is used to introduce a modified heterologous gene into a cell. Such a modified vector may be used in the production of a germline transmitted transgenic animal, or in gene targeting protocols in eukaryotic cells. In particular, high throughput methodology is provided for generating the modified the independent origin based cloning vectors of the present invention.

Abstract translation: 公开了用于修饰重组缺陷宿主细胞中的基因的简单方法。 这样的修饰包括在独立起始基克隆载体中的任何选择的位点产生插入，缺失，取代和/或点突变。 修饰的基因包含在用于将修饰的异源基因引入细胞的独立的起始基克隆载体中。 这种修饰的载体可用于生殖种系传播的转基因动物，或在真核细胞中的基因靶向方案中。 特别地，提供了用于产生本发明的基于独立起源的克隆载体的高通量方法。

公开(公告)号：US06821759B1

公开(公告)日：2004-11-23

申请号：US09619364

申请日：2000-07-19

Applicant: Nathaniel Heintz ,  Peter Model ,  Xiangdong W. Yang ,  Shiaoching Gong

Inventor： Nathaniel Heintz ,  Peter Model ,  Xiangdong W. Yang ,  Shiaoching Gong

IPC: C12N1564

CPC classification number: A01K67/0275 ,  A01K67/0276 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0356 ,  C07K14/4705 ,  C12N15/102 ,  C12N15/64 ,  C12N15/65 ,  C12N15/70 ,  C12N15/8509 ,  C12N15/902 ,  C12N2800/204 ,  C12N2800/30 ,  C12N2840/203 ,  C12N2840/206

Abstract: A simple method for modifying genes in a recombination deficient host cell is disclosed. Such modifications include generating insertions, deletions, substitutions, and/or point mutations at any chosen site in the independent origin based cloning vector. The modified gene is contained in an independent origin based cloning vector that is used to introduce a modified heterologous gene into a cell. Such a modified vector may be used in the production of a germline transmitted transgenic animal, or in gene targeting protocols in eukaryotic cells. In particular, high throughput methodology is provided for generating the modified the independent origin based cloning vectors of the present invention.

Abstract translation: 公开了用于修饰重组缺陷宿主细胞中的基因的简单方法。 这样的修饰包括在独立起始基克隆载体中的任何选择的位点产生插入，缺失，取代和/或点突变。 修饰的基因包含在用于将修饰的异源基因引入细胞的独立的起始基克隆载体中。 这种修饰的载体可用于生殖种系传播的转基因动物，或在真核细胞中的基因靶向方案中。 特别地，提供了用于产生本发明的基于独立起源的克隆载体的高通量方法。