	US 12,031,154 B2
	Universal donor stem cells and related methods
Torsten B. Meissner, Cambridge, MA (US); Leonardo M. R. Ferreira, Cambridge, MA (US); Jack L. Strominger, Cambridge, MA (US); and Chad A Cowan, Cambridge, MA (US)
Assigned to President and Fellows of Harvard College, Cambridge, MA (US)
Filed by President and Fellows of Harvard College, Cambridge, MA (US)
Filed on Nov. 23, 2022, as Appl. No. 17/993,674.
Application 17/148,556 is a division of application No. 15/572,776, granted, now 10,968,426, issued on Apr. 6, 2021, previously published as PCT/US2016/031551, filed on May 9, 2016.
Application 17/993,674 is a continuation of application No. 17/148,556, filed on Jan. 13, 2021, granted, now 11,618,881.
Claims priority of provisional application 62/158,999, filed on May 8, 2015.
Prior Publication US 2023/0303968 A1, Sep. 28, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 5/0735 (2010.01); A61K 39/00 (2006.01); C12N 5/074 (2010.01); C12N 15/86 (2006.01); C12N 15/90 (2006.01)

CPC C12N 5/0606 (2013.01) [A61K 39/001 (2013.01); C12N 5/0696 (2013.01); C12N 15/86 (2013.01); C12N 15/907 (2013.01); C12N 2310/20 (2017.05); C12N 2501/50 (2013.01); C12N 2501/599 (2013.01); C12N 2501/998 (2013.01); C12N 2510/00 (2013.01)]

32 Claims

1. A genetically modified beta cell comprising:

reduced cell surface expression of one or more MHC-I human leukocyte antigen molecules and/or one or more MHC-II human leukocyte antigen molecules relative to an unmodified beta cell; and

increased cell surface expression of one or more tolerogenic factors relative to an unmodified beta cell, wherein a nucleic acid encoding the one or more tolerogenic factors is inserted into at least one allele of a safe harbor locus of the genetically modified beta cell.