公开(公告)号：US06514752B1

公开(公告)日：2003-02-04

申请号：US08443613

申请日：1995-05-18

Applicant: Raju Kucherlapati ,  Beverly H. Koller ,  Oliver Smithies ,  Robert B. Dubridge ,  Gary Greenburg ,  Daniel J. Capon ,  Steven R. Williams ,  Mariona Lourdes Arbones De Rafael

Inventor： Raju Kucherlapati ,  Beverly H. Koller ,  Oliver Smithies ,  Robert B. Dubridge ,  Gary Greenburg ,  Daniel J. Capon ,  Steven R. Williams ,  Mariona Lourdes Arbones De Rafael

IPC: C12N1574

CPC classification number: A01K67/0271 ,  A01K67/0275 ,  A01K67/0276 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/025 ,  A01K2267/03 ,  A01K2267/0381 ,  C07K14/70539 ,  C12N15/00 ,  C12N15/8509

Abstract: Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the &bgr;2-microglobulin gene is inactivated for reducing or eliminating the expression of functional Class I MHC antigens. The resulting cells may be used as universal donor cells. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

Abstract translation: 同源重组用于灭活基因，特别是与MHC抗原相关的基因。 特别地，β2-微球蛋白基因被灭活以减少或消除功能性I类MHC抗原的表达。 所得细胞可用作通用供体细胞。 此外，胚胎干细胞可以通过同源重组来修饰，用于产生嵌合或转基因哺乳动物宿主，其可以用作通用供体器官的来源，或作为药物和移植疗法的模型。 还描述了在非转化的哺乳动物体细胞中同源重组的方法。

公开(公告)号：US6139835A

公开(公告)日：2000-10-31

申请号：US443647

申请日：1995-05-18

Applicant: Raju Kucherlapati ,  Beverly H. Koller ,  Oliver Smithies ,  Robert B. Dubridge ,  Gary Greenburg ,  Daniel J. Capon ,  Steven R. Williams ,  Mariona Lourdes Arbones De Rafael

Inventor： Raju Kucherlapati ,  Beverly H. Koller ,  Oliver Smithies ,  Robert B. Dubridge ,  Gary Greenburg ,  Daniel J. Capon ,  Steven R. Williams ,  Mariona Lourdes Arbones De Rafael

IPC: A01K67/027 ,  A61K35/12 ,  A61K38/21 ,  A61K45/00 ,  C07H21/04 ,  C07K14/74 ,  C12N5/02 ,  C12N5/10 ,  C12N15/00 ,  C12N15/09 ,  C12N15/85 ,  C12Q1/68 ,  G01N33/53 ,  C12N15/63

CPC classification number: A01K67/0271 ,  A01K67/0275 ,  A01K67/0276 ,  C07K14/70539 ,  C12N15/00 ,  C12N15/8509 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/025 ,  A01K2267/03 ,  A01K2267/0381

Abstract: Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the .beta..sub.2- microglobulin gene is inactivated for reducing or eliminating the expression of functional Class I MHC antigens. The resulting cells may be used as allogeneic donor cells. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

Abstract translation: 同源重组用于灭活基因，特别是与MHC抗原相关的基因。 特别地，β2-微球蛋白基因被灭活以减少或消除功能性I类MHC抗原的表达。 所得细胞可用作同种异体供体细胞。 还描述了在非转化的哺乳动物体细胞中同源重组的方法。

公开(公告)号：US5650550A

公开(公告)日：1997-07-22

申请号：US480854

申请日：1995-06-07

Applicant: Kenneth S. Korach ,  Dennis B. Lubahn ,  Oliver Smithies

Inventor： Kenneth S. Korach ,  Dennis B. Lubahn ,  Oliver Smithies

IPC: C07K14/72 ,  C12N15/85 ,  C12N5/00 ,  C12N15/00

CPC classification number: C12N15/8509 ,  A01K67/0276 ,  C07K14/721 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03

Abstract: The present invention provides a mutant non-human vertebrate, in which all or some of the germ and somatic cells contain a mutation in at least one steroid hormone receptor allele, which mutation is introduced into the vertebrate, or an ancestor of the vertebrate, at an embryonic stage, and which mutation produces a phenotype in the vertebrate characterized by a deficit of functional steroid hormone receptors encoded by the allele. Also disclosed are related methods and constructs.

Abstract translation: 本发明提供了一种突变体非人脊椎动物，其中全部或一些细菌和体细胞在至少一种类固醇激素受体等位基因中含有突变，该突变被引入脊椎动物或脊椎动物的祖先， 胚胎期，哪个突变在脊椎动物中产生表型，其特征在于由等位基因编码的功能性类固醇激素受体的缺乏。 还公开了相关的方法和结构。

公开(公告)号：US5574205A

公开(公告)日：1996-11-12

申请号：US175469

申请日：1993-12-30

Applicant: Raju Kucherlapati ,  Beverly H. Koller ,  Oliver Smithies ,  Robert B. Dubridge ,  Gary Greenburg ,  Daniel J. Capon ,  Steven R. Williams ,  Mariona L. A. De Rafael

Inventor： Raju Kucherlapati ,  Beverly H. Koller ,  Oliver Smithies ,  Robert B. Dubridge ,  Gary Greenburg ,  Daniel J. Capon ,  Steven R. Williams ,  Mariona L. A. De Rafael

IPC: A01K67/027 ,  A61K35/12 ,  A61K38/21 ,  A61K45/00 ,  C07H21/04 ,  C07K14/74 ,  C12N5/02 ,  C12N5/10 ,  C12N15/00 ,  C12N15/09 ,  C12N15/85 ,  C12Q1/68 ,  G01N33/53 ,  A61K48/00 ,  A61K49/00 ,  C12N5/00

CPC classification number: A01K67/0271 ,  A01K67/0275 ,  A01K67/0276 ,  C07K14/70539 ,  C12N15/00 ,  C12N15/8509 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/025 ,  A01K2267/03 ,  A01K2267/0381

Abstract: Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, each of the .beta..sub.2- microglobulin gene and the IFN-.gamma.R gene is inactivated for reducing or eliminating the expression of functional MHC antigens. The resulting cells may be used as universal donor cells. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

Abstract translation: 同源重组用于灭活基因，特别是与MHC抗原相关的基因。 特别地，每个β2-微球蛋白基因和IFN-γR基因被灭活以减少或消除功能性MHC抗原的表达。 所得细胞可用作通用供体细胞。 此外，胚胎干细胞可以通过同源重组来修饰，用于产生嵌合或转基因哺乳动物宿主，其可以用作通用供体器官的来源，或作为药物和移植疗法的模型。 还描述了在非转化的哺乳动物体细胞中同源重组的方法。

公开(公告)号：US5416260A

公开(公告)日：1995-05-16

申请号：US611020

申请日：1990-11-09

Applicant: Beverly H. Koller ,  Oliver Smithies

Inventor： Beverly H. Koller ,  Oliver Smithies

IPC: A01K67/027 ,  C07H21/04 ,  C07K14/74 ,  C12N5/10 ,  C12N15/00 ,  C12N15/09 ,  C12N15/85 ,  C12N5/00

CPC classification number: C12N15/8509 ,  A01K67/0271 ,  A01K67/0276 ,  C07K14/70539 ,  C12N15/00 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/025 ,  A01K2267/03

Abstract: Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the .beta..sub.2 -microglobulin gene is inactivated for reducing or eliminating Class I MHC antigens. The resulting cells may be used as universal donors. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs.

Abstract translation: 同源重组用于灭活基因，特别是与MHC抗原相关的基因。 特别地，β2-微球蛋白基因被灭活用于减少或消除I类MHC抗原。 所得细胞可用作通用供体。 此外，胚胎干细胞可以通过同源重组来修饰，用于产生嵌合或转基因哺乳动物宿主，其可以用作通用供体器官的来源。

公开(公告)号：US5413923A

公开(公告)日：1995-05-09

申请号：US990879

申请日：1992-12-11

Applicant: Raju Kucherlapati ,  Beverly H. Koller ,  Oliver Smithies

Inventor： Raju Kucherlapati ,  Beverly H. Koller ,  Oliver Smithies

IPC: A01K67/027 ,  C12N15/00 ,  C12N15/85 ,  C12N5/00

CPC classification number: C12N15/8509 ,  A01K67/0271 ,  A01K67/0276 ,  C12N15/00 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03

Abstract: Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the .beta..sub.2 -microglobulin gene is inactivated for reducing or eliminating Class I MHC antigens. The resulting cells may be used as universal donors. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies.

Abstract translation: 同源重组用于灭活基因，特别是与MHC抗原相关的基因。 特别地，β2-微球蛋白基因被灭活用于减少或消除I类MHC抗原。 所得细胞可用作通用供体。 此外，胚胎干细胞可以通过同源重组来修饰，用于产生嵌合或转基因哺乳动物宿主，其可以用作通用供体器官的来源，或作为药物和移植疗法的模型。