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Application of poly(C)-binding protein 1 (PCBP1) gene or protein regulator thereof to immune system disease

A PCBP1, disease technology, applied in the field of biomedicine, can solve the problems of high price and no targeted pro-inflammatory cytokines

Active Publication Date: 2019-12-06
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Targeting pro-inflammatory cytokines has also become an effective means and important direction for many autoimmune treatments, but there is no effective means of targeting pro-inflammatory cytokines except for monoclonal antibody drugs (which are expensive)

Method used

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  • Application of poly(C)-binding protein 1 (PCBP1) gene or protein regulator thereof to immune system disease
  • Application of poly(C)-binding protein 1 (PCBP1) gene or protein regulator thereof to immune system disease
  • Application of poly(C)-binding protein 1 (PCBP1) gene or protein regulator thereof to immune system disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] Example 1 Screening of autoimmune disease-related factors

[0115]Using a variety of mouse autoimmune models found that GM-CSF produced in CD4+ T cells is the main pathogenic factor of autoimmune diseases, experimental autoimmune encephalomyelitis model (EAE), arthritis models such as CIA or SKG-arthritis model, interstitial lung disease (SKG-ILD) model in SKG mice, etc. Among the subtypes of CD4+ T cells, Th1, Th2, and Th17 can all secrete GM-CSF. Some studies believe that there is a type of CD4+ T cells that only secrete GM-CSF but do not express IFNγ or IL17a at the same time, named ThGM .

[0116] Th1 cells are a subtype of CD4+ T cells that mainly express IFNγ, and the GM-CSF secreted by them has been proved to be necessary for the pathogenesis of EAE; Th17 cells are a subtype of CD4+ T cells that mainly express IL17, which was first thought to cause inflammation by secreting IL17 And autoimmune diseases, and studies have found that knockout or antibody neutraliz...

Embodiment 2

[0118] Embodiment 2 GM-CSF related gene screening

[0119] Post-transcriptional regulation plays an important role in the expression process of GM-CSF, and the stability of GM-CSF mRNA determines its expression level. The regulation at the post-transcriptional level must rely on RNA-binding proteins to function. At least 1500 RNA-binding proteins have been found in the human genome, and the expression of many RNA-binding proteins has tissue and spatiotemporal specificity. Through the detection of high-throughput sequencing data (GSE48138), it was found that nearly 100 RNA-binding proteins were highly expressed in T lymphocytes or had a dynamic trend, suggesting that they may have functions in T lymphocytes.

Embodiment 3

[0120] Example 3 Screening of Lymphocyte-specific RNA Binding Proteins

[0121] 3.1 Construction of RNA-binding protein library

[0122] According to the results in Example 2, nearly 100 RNA-binding proteins related to the development and differentiation of lymphocytes were screened out, and an shRNA library was established. Among them, the 80 RNA-binding proteins most correlated with the RNA-binding domain are shown in Table 2 , and design shRNAs for it, a total of about 300 shRNAs.

[0123] Table 2: RNA-binding proteins used for shRNA screening

[0124]

[0125] 3.2 RNA binding protein knockdown screening

[0126] In view of the shortcomings of primary effector T cells, such as long differentiation time and inability to proliferate in large quantities, Jurkat cells (human peripheral blood leukemia T cells, purchased from the Cell Resource Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences) were selected to establish a screening model.

[0...

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Abstract

The invention provides application of a poly(C)-binding protein 1 (PCBP1) gene or a protein regulator thereof to an immune system disease, and particularly relates to application of a PCBP1 regulatorto the immune system disease, in particular to application of a PCBP1 inhibitor to an autoimmune disease.

Description

technical field [0001] The invention belongs to the field of biomedicine. Specifically, it relates to the application of poly(C)-binding protein 1 (poly(C)-binding protein 1, PCBP1) modulators in immune system diseases; more specifically, poly(C)-binding protein 1 (poly(C)-binding protein 1. Application of PCBP1) inhibitors in autoimmune diseases. Background technique [0002] Autoimmune diseases are a type of diseases in which the body's immune system mistakenly recognizes its own organs, tissues and cells, induces an immune response, and then causes self-injury. Its incidence rate is as high as 5%-8% in the whole population, and it is the third major disease after cardiovascular diseases and tumors. At present, there are about 100 autoimmune diseases that have been diagnosed. Common autoimmune diseases include: multiple sclerosis (MS), rheumatoid arthritis (RA), autoimmune myocarditis, systemic lupus erythematosus (SLE), type I Diabetes, autoimmune thyroiditis, psoriasi...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61P29/00A61P37/02
CPCA61K45/00A61P29/00A61P37/02
Inventor 常兴王志章
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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