Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6916654

Title:Universal donor cells
Inventors:Sims, Peter J.; Mequon, WI, USA
Bothwell, Alfred L. M.; Guilford, CT, USA
Elliot, Eileen A.; New Haven, CT, USA
Flavell, Richard A.; Killingworth, CT, USA
Madri, Joseph; North Branford, CT, USA
Rollins, Scott; Monroe, CT, USA
Bell, Leonard; Woodbridge, CT, USA
Squinto, Stephen; Irvington, NY, USA
Summary:This invention describes genetically engineered mammalian cells for the treatment of coronary artery disease. Such genetically engineered cells include a coding region which provides protection against complement-based lysis such as hyperacute rejection, and can therefore serve as universal donor cells in such applications as reconstruction of vascular linings or in the administration of therapeutic agents. Further disclosed are methods by which the cell's natural genome is changed so that functional proteins encoded by either the class II or both the class I and the class II major histocompatibility complex genes do not appear on the cell's surface, thereby precluding attack by the T-cells. Also described is an optional self-destruction mechanism such that the cells can be removed from the host when no longer needed. Further disclosed are nucleotide molecules expressed by the isolated, genetically engineered mammalian cell, such that the nucleotide molecules are heterologous or located at separate loci from the native complement regulator sequence, in an amount effective to inhibit complement-mediated attack of the engineered cell when introduced into an animal of another species or another individual.
Abstract:Genetically engineered cells are provided which can serve as universal donor cells in such applications as reconstruction of vascular linings or the administration of therapeutic agents. The cells include a coding region which provides protection against complement-based lysis, i.e., hyperacute rejection. In addition, the cell's natural genome is changed so that functional proteins encoded by either the class II or both the class I and the class II major histocompatibility complex genes do not appear on the cell's surface. In this way, attack by T-cells is avoided. Optionally, the cells can include a self-destruction mechanism so that they can be removed from the host when no longer needed.
US Patent Website:Click Here for Full Text of Patent
Title Number:US6916654
Application Number:US2000000566254
Date Filed:05/05/2000
Date Published:12/07/2005
Assignee:Oklahoma Medical Research Foundation, Oklahoma City, OK, USA


 
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