Universal cell and preparation method therefor
AssigneeXellsmart Bio-Pharmaceutical (Suzhou) Co., Ltd.
InventorsXiang LI, Minzhe ZHU
Life of this patent
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Abstract
Disclosed are a universal cell and a preparation method therefor. After major histocompatible complex MHC-I and II genes are inactivated in cells, at least one protein of SLC35A1, GNE, CMAS, ST3Gal5, ST8SIA1, MUC1, APMAP, SMAGP, and CD43 is overexpressed, so that the obtained human pluripotent stem cells or human cell lines can further escape the killing of NK cells and macrophages on the basis of escaping the attack of T cells. Meanwhile, the low-immunogenicity pluripotent stem cells retain the stemness and differentiation capacity thereof.
Claims45
A universal cell, relative to a wild-type cell, comprising:
- 1) reduced expression or absent expression of MHC-I and/or MHC-II human leukocyte antigens, and
- 2) an expression sequence of at least one of SLC35A1, GNE, CMAS, ST3Gal5, ST8SIA1, MUC1, APMAP, SMAGP, and CD43 genes, with the expression level of the gene being increased, wherein
- the cell is capable of escaping the attack by T cells and the killing by NK cells and macrophages.
A cell having increased expression of at least one of SLC35A1, GNE, CMAS, ST3Gal5, ST8SIA1, MUC1, APMAP, SMAGP, and CD43 proteins, and reduced expression or absent expression of MHC class I and/or MHC class II human leukocyte antigens, wherein
- preferably, the cell expresses at least one of MUC1, APMAP, and CD43 proteins;
- further preferably, the cell expresses CD43.
A cell having absent expression of CIITA, increased expression of at least one of SLC35A1, GNE, CMAS, ST3Gal5, ST8SIA1, MUC1, APMAP, SMAGP, and CD43 proteins, and reduced expression or absent expression of MHC class I and/or MHC class II human leukocyte antigens.
A cell having absent expression of B2M, increased expression of any one of SLC35A1, GNE, CMAS, ST3Gal5, ST8SIA1, MUC1, APMAP, SMAGP, or CD43 protein, and reduced expression or absent expression of MHC class I and/or MHC class II human leukocyte antigens, wherein
- preferably, the cell expresses at least one of MUC1, APMAP, and CD43 proteins;
- further preferably, the cell expresses CD43.
A cell having absent expression of CIITA and B2M, increased expression of at least one of SLC35A1, GNE, CMAS, ST3Gal5, ST8SIA1, MUC1, APMAP, SMAGP, and CD43 proteins, and reduced expression or absent expression of MHC class I and/or MHC class II human leukocyte antigens, wherein
- preferably, the cell expresses at least one of MUC1, APMAP, and CD43 proteins;
- further preferably, the cell expresses CD43.
A cell having increased expression of at least one of SLC35A1, GNE, CMAS, ST3Gal5, ST8SIA1, MUC1, APMAP, SMAGP, and CD43 proteins, and at least one polypeptide selected from DUX4, CD27, CD35, CD200, HLA-C, PD-L1, CD47, CD24, CD26, CCL21, Mfge8, and SerpinB9, and reduced expression or absent expression of MHC class I and/or MHC class II human leukocyte antigens, wherein
- preferably, the cell expresses at least one of MUC1, APMAP, and CD43 proteins;
- further preferably, the cell expresses CD43.
A cell having absent expression of CIITA, increased expression of at least one of SLC35A1, GNE, CMAS, ST3Gal5, ST8SIA1, MUC1, APMAP, SMAGP, and CD43 proteins, and at least one polypeptide selected from DUX4, CD27, CD35, CD200, HLA-C, PD-L1, CD47, CD24, CD26, CCL21, Mfge8, and SerpinB9, and reduced expression or absent expression of MHC class I and/or MHC class II human leukocyte antigens, wherein
- preferably, the cell expresses at least one of MUC1, APMAP, and CD43 proteins;
- further preferably, the cell expresses CD43.
A cell having absent expression of B2M, increased expression of at least one of SLC35A1, GNE, CMAS, ST3Gal5, ST8SIA1, MUC1, APMAP, SMAGP, and CD43 proteins, and at least one polypeptide selected from DUX4, CD27, CD35, CD200, HLA-C, PD-L1, CD47, CD24, CD26, CCL21, Mfge8, and SerpinB9, and reduced expression or absent expression of MHC class I and/or MHC class II human leukocyte antigens, wherein
- preferably, the cell expresses at least one of MUC1, APMAP, and CD43 proteins;
- further preferably, the cell expresses CD43.
A cell having absent expression of CIITA and B2M, increased expression of at least one of SLC35A1, GNE, CMAS, ST3Gal5, ST8SIA1, MUC1, APMAP, SMAGP, and CD43 proteins, and at least one polypeptide selected from DUX4, CD27, CD35, CD200, HLA-C, PD-L1, CD47, CD24, CD26, CCL21, Mfge8, and SerpinB9, and reduced expression or absent expression of MHC class I and/or MHC class II human leukocyte antigens, wherein
- preferably, the cell expresses at least one of MUC1, APMAP, and CD43 proteins;
- further preferably, the cell expresses CD43.
Dependencies are inferred from the claim text.