Pluripotent stem cell for expressing shRNA (short hairpin ribonucleic acid) and/or shRNA-miR of targeted IgE (immunoglobulin E) or derivative thereof

Abstract

The invention discloses a pluripotent stem cell for expressing shRNA (short hairpin ribonucleic acid) and/or shRNA-miR (short hairpin ribonucleic acid-miR) targeting IgE (immunoglobulin E) or a derivative of the pluripotent stem cell. An expression sequence of the shRNA and/or the shRNA-miR targeting IgE is introduced into a genome of the pluripotent stem cell or the derivative of the pluripotent stem cell. After shRNA and/or shRNA-miR of targeting IgE expressed by the pluripotent stem cell or the derivative of the pluripotent stem cell are/is wrapped by exosome, the exosome carries the effect RNA molecules to be combined with the target cell, and then the target cell is released, so that the expression of the IgE is inhibited, and the shRNA and/or the shRNA-miR can be used for treating allergy, asthma and other related diseases.

Description

technical field [0001] The invention belongs to the technical field of genetic engineering, and in particular relates to a pluripotent stem cell or a derivative thereof expressing shRNA and / or shRNA-miR targeting IgE. Background technique [0002] IgE (Immunoglobulin E) is a secreted immunoglobulin consisting of two light chains and two heavy chains. It is produced by the plasma cells of the lamina propria in the nasopharynx, tonsils, bronchi, and gastrointestinal mucosa, and is the main antibody that causes type I allergy. In patients with allergic constitution or hypersensitivity, serum IgE is significantly higher than that in normal people, and patients with exogenous asthma are several times higher than normal people. Therefore, high levels of IgE in serum often indicate genetic allergy, or the existence of type I allergy. Therefore, IgE has become a new target for the treatment of allergy and asthma, and IgE blockers (anti-IgE antibodies) can be used as allergy and as...

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 have not been better resolved

[0009] 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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