公开(公告)号：EP2958990A4

公开(公告)日：2016-07-13

申请号：EP14754746

申请日：2014-02-20

申请人： REGENERON PHARMA

发明人： LEE JEFFREY D ,  AUERBACH WOJTEK ,  HESLIN DAVID ,  FRENDEWEY DAVID ,  LAI KA-MAN VENUS ,  VALENZUELA DAVID M

IPC分类号： C12N5/07 ,  A01K67/027 ,  A61D19/04 ,  C12N5/00 ,  C12N5/02 ,  C12N5/0735 ,  C12N5/10 ,  C12N15/85

CPC分类号： C12N15/8509 ,  A01K67/02 ,  A01K67/0271 ,  A01K67/0275 ,  A01K2207/12 ,  A01K2217/15 ,  A01K2227/105 ,  A61D19/04 ,  C12N5/0606 ,  C12N15/8775 ,  C12N2501/235 ,  C12N2501/727 ,  C12N2501/999 ,  C12N2510/00

摘要： Compositions and methods are provided for making rat pluripotent and totipotent cells, including rat embryonic stem (ES) cells. Compositions and methods for improving efficiency or frequency of germline transmission of genetic modifications in rats are provided. Such methods and compositions comprise an in vitro culture comprising a feeder cell layer and a population of rat ES cells or a rat ES cell line, wherein the in vitro culture conditions maintain pluripotency of the ES cell and comprises a media having mouse leukemia inhibitor factor (LIF) or an active variant or fragment thereof. Various methods of establishing such rat ES cell lines are further provided. Methods of selecting genetically modified rat ES cells are also provided, along with various methods to generate a transgenic rat from the genetically modified rat ES cells provided herein. Various kits and articles of manufacture are further provided.

摘要翻译： 提供组合物和方法用于制备大鼠多能全细胞，包括大鼠胚胎干（ES）细胞。 提供了用于提高大鼠遗传修饰的种系传播效率或频率的组合物和方法。 这样的方法和组合物包括体外培养物，其包含饲养细胞层和大鼠ES细胞群或大鼠ES细胞系，其中体外培养条件保持ES细胞的多能性，并且包含具有小鼠白血病抑制因子 LIF）或其活性变体或片段。 进一步提供了建立这种大鼠ES细胞系的各种方法。 还提供了选择遗传修饰的大鼠ES细胞的方法，以及从本文提供的遗传修饰的大鼠ES细胞产生转基因大鼠的各种方法。 还提供了各种套件和制品。

公开(公告)号：EP2986729A4

公开(公告)日：2016-10-19

申请号：EP14784879

申请日：2014-04-16

申请人： REGENERON PHARMA

发明人： LEE JEFFREY D ,  MUJICA ALEXANDER O ,  AUERBACH WOJTEK ,  LAI KA-MAN VENUS ,  VALENZUELA DAVID M ,  YANCOPOULOS GEORGE D

IPC分类号： C12N15/85 ,  C12N9/22

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.