Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US5574205

Title:Homologous recombination for universal donor cells and chimeric mammalian hosts
Inventors:Kucherlapati, Raju; Darien, CT, USA
Koller, Beverly H.; Carrboro, NC, USA
Smithies, Oliver; Chapel Hill, NC, USA
Dubridge, Robert B.; Belmont, CA, USA
Greenburg, Gary; San Carlos, CA, USA
Capon, Daniel J.; Hillsborough, CA, USA
Williams, Steven R.; San Francisco, CA, USA
De Rafael, Mariona L. A.; Barcelona, Spain
Summary:Described herein is a method of producing genetically engineered mammalian cells lacking functional major histocompatibility (MHC) antigens. The invention relates to homologous recombination as it is employed to inactivate genes, particularly genes associated with MHC antigens such that each of the beta 2- microglobulin gene and the IFN- gamma R gene is inactivated for reducing or eliminating the expression of functional MHC antigens. Further disclosed are methods for the production of a genetically engineered mouse lacking functional Class I and II MHC antigens. Additional claims of the invention include embryonic stem cells and methods by which they may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which in turn may be used as sources of universal donor organs, or as models for drug and transplantation therapies. Also provided are methods for homologous recombination in non-transformed mammalian somatic cells. Therapeutic applications are included for use as universal donor cells and for diminishing immune rejection in transplantation.
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.
US Patent Website:Click Here for Full Text of Patent
Title Number:US5574205
Application Number:US1993000175469
Date Filed:30/12/1993
Date Published:12/11/1996
Assignee:Cell Genesys, Foster City, CA, USA


 
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