Universal donor stem cells and related methods
AssigneePresident and Fellows of Harvard College
InventorsTorsten B. Meissner, Leonardo M.R. Ferreira, Jack L. Strominger, Chad A. Cowan
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Abstract
Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein do not express one or more MHC-I and MHC-II human leukocyte antigens. Similarly, in certain embodiments, the universal donor stem cells disclosed herein do not express one or more human leukocyte antigens (e.g., HLA-A, HLA-B and/or HLA-C) corresponding to MHC-I and MHC-II human leukocyte antigens, thereby rendering such cells hypoimmunogenic.
Claims21
A method of generating a genetically modified stem cell comprising:
- (i) introducing one or more genetic modifications into a stem cell that reduce cell surface expression of one or more MHC-I human leukocyte antigen molecules relative to an unmodified cell of the same type and/or one or more genetic modifications that reduce cell surface expression of one or more MHC-II human leukocyte antigen molecules relative to an unmodified cell of the same type, and
- (ii) introducing a nucleic acid encoding CD47 into the stem cell,
- wherein the stem cell is an embryonic stem cell or an induced pluripotent stem cell, and
- wherein the genetically modified stem cell comprises one or more genetic modifications that reduce cell surface expression of one or more MHC-I human leukocyte antigen molecules relative to an unmodified cell of the same type and/or one or more genetic modifications that reduce cell surface expression of one or more MHC-II human leukocyte antigen molecules relative to an unmodified cell of the same type, and comprise a nucleic acid encoding CD47.
Dependencies are inferred from the claim text.