Pluripotent stem cell expressing IgE (Immunoglobulin E) blocker or derivative of pluripotent stem cell and application

Abstract

The invention discloses a pluripotent stem cell for expressing an IgE (Immunoglobulin E) blocker or a derivative of the pluripotent stem cell and application, an expression sequence of the IgE blocker is introduced into a genome of the pluripotent stem cell or the derivative of the pluripotent stem cell, and the IgE blocker is an anti-IgE antibody. The pluripotent stem cell expressing the IgE blocker or the derivative of the pluripotent stem cell can be applied to low-immunogenicity cells such as iPSCs (induced pluripotent stem cells) induced by autologous cells or differentiated into MSCs (mesenchymal stem cells), can continuously express the IgE blocker in vivo, and is used for resisting allergy and / or treating asthma and related diseases.

Description

technical field [0001] The invention belongs to the technical field of genetic engineering, and specifically relates to a pluripotent stem cell expressing an IgE blocker or a derivative thereof and an application thereof. Background technique [0002] IgE (immunoglobulin E) is a secreted immunoglobulin consisting of two light chains and two heavy chains. It is produced by plasma cells in the lamina propria of the nasopharynx, tonsils, bronchi, and gastrointestinal mucosa, and is the main antibody that causes type I allergic reactions. In patients with allergic constitution or hypersensitivity, serum IgE is significantly higher than that of normal people, and in patients with exogenous asthma is several times higher than that of normal people. Therefore, if the IgE content in the serum is too high, it often indicates the presence of genetic allergies or type I allergy. Therefore, IgE has become a new target for the treatment of allergy and asthma, and IgE blockers (anti-IgE...

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 least two rounds of single-cell isolation and culture for each gene editing, the whole process requires at least six rounds of single-cell isolation and culture. Cell separation and culture, these processes are inevitable and highly probable due to multiple gene editing off-targets or chromatin instability, or various unpredictable mutations in cells due to a large number of single-cell passages and proliferations, which in turn induce various problems such as carcinogenesis and metabolic diseases

It can be seen that this type of immune compatibility program is also an expedient measure in the "transitional period", and there are still many problems that cannot be solved better

[0008] In addition, some people have designed to induce killing of donor tissues and cells after they become diseased by inducing suicide genes. The loss of suitable donor cells, tissues and organs after killing is another big problem

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