HLA G-modified cells and methods
First Claim
1. A genetically modified mammalian cell that has reduced immunogenicity and/or improved immunosuppression as compared to the mammalian cell without said genetic modification, whereinthe genetically modified mammalian cell comprises in its genome an exogenous nucleic acid comprising:
- (a) a nucleic acid sequence encoding a Human leukocyte antigen-G (HLA-G) protein comprising a full length amino acid sequence of SEQ ID NO;
2 operably linked to an Elongation Factor-1 alpha (EF-1α
) promoter comprising the sequence of SEQ ID NO;
6; and
(b) a 3′
untranslated region (UTR) comprising a full length nucleotide sequence of SEQ ID NO;
3;
whereinthe genetically modified mammalian cell is selected from the group consisting of embryonic stem cell, embryonic epidermal progenitors and human dermal fibroblast cells, and wherein the encoded HLA-G protein is expressed by the genetically modified mammalian cell for at least seven weeks.
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Accused Products
Abstract
Disclosed herein are genetically modified cells expressing HLA-G (e.g., cell surface HLA-G) persistently, and nucleic acid compositions useful for generating such genetically modified cells. Also disclosed are cell therapy methods that utilize genetically modified cells that express HLA-G persistently. The HLA-G genetic modifications described herein provide the cells with characteristics of reduced immunogenicity and/or improved immunosuppression, such that these cells have the promise of being universal or improved donor cells for transplants, cellular and tissue regeneration or reconstruction, and other therapies.
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Citations
12 Claims
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1. A genetically modified mammalian cell that has reduced immunogenicity and/or improved immunosuppression as compared to the mammalian cell without said genetic modification, wherein
the genetically modified mammalian cell comprises in its genome an exogenous nucleic acid comprising: - (a) a nucleic acid sequence encoding a Human leukocyte antigen-G (HLA-G) protein comprising a full length amino acid sequence of SEQ ID NO;
2 operably linked to an Elongation Factor-1 alpha (EF-1α
) promoter comprising the sequence of SEQ ID NO;
6; and
(b) a 3′
untranslated region (UTR) comprising a full length nucleotide sequence of SEQ ID NO;
3;
whereinthe genetically modified mammalian cell is selected from the group consisting of embryonic stem cell, embryonic epidermal progenitors and human dermal fibroblast cells, and wherein the encoded HLA-G protein is expressed by the genetically modified mammalian cell for at least seven weeks. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
- (a) a nucleic acid sequence encoding a Human leukocyte antigen-G (HLA-G) protein comprising a full length amino acid sequence of SEQ ID NO;
Specification