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公开(公告)号：US20240298619A1
公开(公告)日：2024-09-12
申请号：US18316461
申请日：2023-05-12
IPC分类号： A01K67/0278 , A61K49/00 , C07K14/435 , C07K14/47 , C07K16/28 , C12Q1/6886 , G01N33/50
CPC分类号： A01K67/0278 , A61K49/0008 , C07K14/4747 , C07K16/2803 , C12Q1/6886 , G01N33/5038 , A01K2207/15 , A01K2217/05 , A01K2217/072 , A01K2227/105 , A01K2267/0331 , C07K14/435 , C07K2319/00 , C07K2319/02 , C07K2319/03 , C12Q2600/106 , C12Q2600/158 , G01N2333/57 , G01N2333/70503 , G01N2500/10
摘要： Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Programmed cell death 1 (Pdcd1) gene. The non-human animals, in some embodiments, comprise a genetic modification to an endogenous Pdcd1 gene so that the non-human animals express a PD-1 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).
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公开(公告)号：US20230172172A1
公开(公告)日：2023-06-08
申请号：US18159414
申请日：2023-01-25
发明人： Andrew J. Murphy , Alexander O. Mujica , Ka-Man Venus Lai , Sokol Haxhinasto , Zaruhi Hovhannisyan
IPC分类号： A01K67/027 , C07K16/24 , C07K16/28 , C12N15/85
CPC分类号： A01K67/0278 , C07K16/244 , C07K16/2866 , C12N15/8509 , A01K2207/15 , A01K2217/072 , A01K2227/105 , C07K2317/24 , C07K2317/76 , C12N2015/8527 , A01K2267/0368 , A01K2217/15
摘要： This disclosure relates to genetically modified rodent animals and rodent models of human diseases. More specifically, this disclosure relates to genetically modified rodents whose genome comprises a humanized Il1rl2 gene (coding for the IL1rl2 subunit of the IL-36R protein) and human IL-36α, β and γ ligand genes. The genetically modified rodents disclosed herein display enhanced skin and intestinal inflammation as a preclinical model of psoriasis and IBD, respectively, and serve as a rodent model of human DITRA disease.
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公开(公告)号：US20200154684A1
公开(公告)日：2020-05-21
申请号：US16625168
申请日：2018-06-27
发明人： Alexander O. Mujica , Viktoria Gusarova , Cheng Wang , Christos Kyratsous , Terra Potocky , Katherine Cygnar , Joel Martin
IPC分类号： A01K67/027 , A61K49/00 , C07K14/705
摘要： Non-human animal cells and non-human animals comprising a humanized Asgr1 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 Asgr1 locus express a human ASGR1 protein or an Asgr1 protein, fragments of which are from human ASGR1. Methods are provided for using such non-human animals comprising a humanized Asgr1 locus to assess in vivo efficacy of human-ASGR1-mediated delivery of therapeutic molecules or therapeutic complexes to the liver and to assess the efficacy of therapeutic molecules or therapeutic complexes acting via human-ASGR1-mediated mechanisms.
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公开(公告)号：US10070632B2
公开(公告)日：2018-09-11
申请号：US15442857
申请日：2017-02-27
发明人： Lisa Purcell , Alexander O. Mujica , Yajun Tang
IPC分类号： A01K67/027 , C12N5/0735 , C12N9/64
CPC分类号： A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2227/10 , A01K2227/105 , A01K2267/0337 , A61K48/00 , C07K14/47 , C07K2319/00 , C12N5/0606 , C12N9/6424 , C12N15/09 , C12N15/63 , C12N15/86 , C12N2710/10332
摘要： Genetically modified rodents such as mice and rats, and methods and compositions for making and using the same, are provided. The rodents comprise a humanization of at least one endogenous rodent Tmprss gene, such as an endogenous rodent Tmprss2, Tmprss4, or Tmprss11d gene.
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公开(公告)号：US20170245482A1
公开(公告)日：2017-08-31
申请号：US15442857
申请日：2017-02-27
发明人： Lisa Purcell , Alexander O. Mujica , Yajun Tang
IPC分类号： A01K67/027 , C12N5/0735
CPC分类号： A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2227/10 , A01K2227/105 , A01K2267/0337 , A61K48/00 , C07K14/47 , C07K2319/00 , C12N5/0606 , C12N9/6424 , C12N15/09 , C12N15/63 , C12N15/86 , C12N2710/10332
摘要： Genetically modified rodents such as mice and rats, and methods and compositions for making and using the same, are provided. The rodents comprise a humanization of at least one endogenous rodent Tmprss gene, such as an endogenous rodent Tmprss2, Tmprss4, or Tmprss11d gene.
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公开(公告)号：US20140309487A1
公开(公告)日：2014-10-16
申请号：US14314866
申请日：2014-06-25
发明人： Jeffrey D. Lee , Alexander O. Mujica , Wojtek Auerbach , Ka-Man Venus Lai , David M. Valenzuela , George D. Yancopoulos
CPC分类号： C12N15/8509 , A01K67/0276 , A01K67/0278 , A01K2217/07 , A01K2227/105 , A01K2267/0362 , A01K2267/0381 , A61D19/04 , C07K14/7155 , C07K14/775 , C12N15/907 , C12N2015/8527 , C12N2800/30 , C12N2810/00
摘要： Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.
摘要翻译： 提供组合物和方法用于使用包含如本文所述的各种内源或外源核酸序列的大靶向载体（LTVEC）修饰目标大鼠基因组座位。 还提供了用于产生在其种系中包含一个或多个靶向遗传修饰的转基因大鼠的组合物和方法。 提供了组合物和方法，其包含在大鼠白细胞介素-2受体γ基因座，大鼠ApoE基因座，大鼠Rag2基因座，大鼠Rag1基因座和/或大鼠Rag2 / Rag1基因座。 本文提供的各种方法和组合物允许这些修饰的基因座通过种系传播。
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公开(公告)号：US12096754B2
公开(公告)日：2024-09-24
申请号：US17388111
申请日：2021-07-29
IPC分类号： A01K67/0278 , A01K67/0276 , A61K49/00 , C07K14/705 , C07H21/04 , C12N15/63 , C12N15/79
CPC分类号： A01K67/0278 , A01K67/0276 , A61K49/0008 , C07K14/70503 , A01K2207/15 , A01K2217/072 , A01K2217/075 , A01K2217/15 , A01K2227/105 , A01K2267/01 , A01K2267/03 , A01K2267/0331 , C07H21/04 , C12N15/63 , C12N15/79 , C12N2510/00 , C12N2517/02
摘要： Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Lymphocyte activation gene 3 (Lag3). The non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous Lag3 locus so that the non-human animals express a Lag3 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).
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公开(公告)号：US20210301301A1
公开(公告)日：2021-09-30
申请号：US17196408
申请日：2021-03-09
发明人： Jeffrey D. Lee , Alexander O. Mujica , Wojtek Auerbach , Ka-Man Venus Lai , David M. Valenzuela , George D. Yancopoulos
IPC分类号： C12N15/85 , A61D19/04 , A01K67/027 , C07K14/715 , C07K14/775 , C12N15/90
摘要： Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.
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公开(公告)号：US10975390B2
公开(公告)日：2021-04-13
申请号：US16451859
申请日：2019-06-25
发明人： Jeffrey D. Lee , Alexander O. Mujica , Wojtek Auerbach , Ka-Man Venus Lai , David M. Valenzuela , George D. Yancopoulos
IPC分类号： C12N15/85 , A61D19/04 , A01K67/027 , C07K14/715 , C07K14/775 , C12N15/90
摘要： Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.
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公开(公告)号：US20200370054A1
公开(公告)日：2020-11-26
申请号：US16986077
申请日：2020-08-05
发明人： David Heslin , Roxanne Ally , Chia-Jen Siao , Ka-Man Venus Lai , David M. Valenzuela , Chunguang Guo , Michael LaCroix-Fralish , Lynn Macdonald , Aarti Sharma-Kanning , Daisuke Kajimura , Gustavo Droguett , David Frendewey , Alexander O. Mujica
IPC分类号： C12N15/62 , A01K67/027 , C12N15/113 , C12N15/90 , C12N5/0793 , C12N5/0797
摘要： 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.
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