Immunocompatible reversible universal pluripotent stem cells and application thereof

A kind of pluripotent stem cell and general-purpose technology, which is applied in immunocompatibility and reversible general-purpose pluripotent stem cell and its application field, can solve the problems of high risk of disease, no better solution to the problem, shrinking of antigen integrity and other problems, and achieve functional The effect of both sex and safety

Pending Publication Date: 2021-02-09
FUTURE HOMO SAPIENS INST OF REGENERATIVE MEDICINE CO LTD (FHSR) +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, for this kind of cells, firstly, the types of antigens presented by HLA-I antigens are reduced by more than two-thirds, and the integrity of the antigens that can be presented is greatly and irreversibly reduced. For various tumors, viruses and other disease antigens The presentation is highly biased, and still retains a considerable degree of risk of tumorigenesis and viral infection, and the risk of disease is higher when CIITA is knocked out at the same time; secondly, 12 high-frequency immune types The ethnic differences of HLA-C antigens are very large, and only 70% of them can be accounted for in some areas through our verification and calculation. However, China, India and other populous countries do not yet have authoritative large-sample HLA data. The use of PSCs is still subject to the test of a huge matching gap; third, this method will undergo several repeated gene editing work, and at le

Method used

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  • Immunocompatible reversible universal pluripotent stem cells and application thereof
  • Immunocompatible reversible universal pluripotent stem cells and application thereof
  • Immunocompatible reversible universal pluripotent stem cells and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0117] Example 1 A preparation method of immune compatible and reversible universal pluripotent stem cells and derivatives thereof

[0118] A method for preparing immune-compatible and reversible general-purpose pluripotent stem cells or derivatives thereof, wherein an inducible gene expression system and at least one immune-compatible molecule expression sequence are introduced into the genome of the pluripotent stem cells or their derivatives; The compatible molecule is used to regulate the expression of genes related to immune response in the pluripotent stem cell or its derivative; and the expression of the immune compatible molecule is regulated by an inducible gene expression system.

[0119] When carrying out immune-compatibility transformation, the transformation can be carried out on hPSCs first, and then differentiated into derivatives of pluripotent stem cells for use after the transformation is completed; it is also possible to carry out immune-compatibility transfo...

Embodiment 2

[0350] Using the method of Example 1, the Tet-Off system and immune compatibility molecule combination (Table 3-Table 6) were knocked into the genomic safety site AAVS1 of hPSCs-derived EBs to obtain EB immune-compatible cells.

[0351] use 51 Cr release test to detect the immune compatibility effect of EB ball immunocompatibility cells and T cells:

[0352] 1. Digest EB immune-compatible cells into individual cells as target cells;

[0353] 2. Will pass 51 Cr-labeled target cells and T cells were added to a 96-well culture plate at a ratio of 1:5 for post-reaction detection;

[0354] 3. According to 51 Detection of Cell Specificity of Immunocompatible Cells in EB Balloons by Cr Release Assay 51 Cr release rate, the results are shown in Table 9 and Figure 8 shown.

[0355] Table 9 EB ball immune compatible cells 51 Cr release rate

[0356]

[0357]

[0358] From Table 9 and Figure 8 It can be seen that the immunocompatibility effect of the hPSCs-derived EB sph...

Embodiment 3

[0360] This embodiment will test the effect of using an inducer (Dox) to prevent expression of the knocked-in immune-compatibility molecule in the case of graft lesions, and the steps are as follows:

[0361] (1) Add 6uM Dox to the culture medium of the EB sphere immunocompatibility cells prepared in Example 2 and treat for 48h;

[0362] (2) Digest the Dox-treated EB immune-compatible cells into individual cells as target cells;

[0363] (3) will pass 51 Cr-labeled target cells and T cells were added to a 96-well culture plate at a ratio of 1:5 for post-reaction detection;

[0364] (4) According to 51 Detection of Cell Specificity of Immunocompatible Cells in EB Balloons by Cr Release Assay 51 Cr release rate, the results are shown in Table 10 and Figure 9 shown.

[0365] Table 10 EB ball immune compatible cells after Dox treatment 51 Cr release rate

[0366]

[0367]

[0368] from Table 10 and Figure 9 It can be seen that after the hPSCs-derived EB sphere immuno...

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Abstract

The invention discloses immunocompatible reversible universal pluripotent stem cells or derivatives thereof. An inducible gene expression system and an expression sequence of at least one immunocompatible molecule are introduced into the genome of the pluripotent stem cells or the derivatives thereof. The immunocompatible molecules are used for regulating and controlling the expression of genes related to immune response in pluripotent stem cells or derivatives of the pluripotent stem cells. The expression of the immunocompatible molecule is regulated and controlled by an inducible gene expression system. According to the technical scheme, the immunocompatibility between the graft and the receptor can be improved, and the antigen presentation capability of graft cells can be reversibly recovered, so that the clinical safety of such universal pluripotent stem cells and derivatives is improved, and the clinical application value of the universal pluripotent stem cells and derivatives isgreatly expanded.

Description

technical field [0001] The invention belongs to the technical field of genetic engineering, and in particular relates to an immune-compatible and reversible universal pluripotent stem cell and its application. Background technique [0002] Stem cells are a type of "seed" cells with the ability to self-renew and differentiate into specific functional somatic cells. They have the potential to regenerate into various tissues and organs and the human body, and play an important role in major biological activities such as immune response, aging, and tumorigenesis. core and irreplaceable role. According to the degree of stem cell characteristics, stem cells are mainly divided into: totipotent stem cells (Totipotent stem cells), pluripotent stem cells (Pluripotent stem cells, PSCs) and adult stem cells (adult stem cells). [0003] Among them, pluripotent stem cells (PSCs) have almost unlimited self-renewal ability and the potential to develop and differentiate into organs, tissues...

Claims

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Application Information

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IPC IPC(8): C12N5/10C12N15/85
CPCC12N5/0606C12N5/0603C12N5/0608C12N5/0693C12N5/0696C12N15/85C12N15/113C07K14/70521C07K14/70539C07K14/70532C07K14/70503C12N2510/00C12N2830/006C12N2310/14A61K35/545A61K35/17C12N2310/20C12N5/0646C12N2506/02C12N2310/141
Inventor 王淋立陈月花杨建国莫健
Owner FUTURE HOMO SAPIENS INST OF REGENERATIVE MEDICINE CO LTD (FHSR)
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