Application of RBPJ as drug target in preparation of drug for inhibiting T cell depletion

A cell, drug technology, applied in the field of medicine

Active Publication Date: 2021-01-29
WEST CHINA HOSPITAL SICHUAN UNIV
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This technology has been widely used in the identification of cell types in normal organs, organ development, tumorigenesis, etc., but there are few reports on the screening of targets that inhibit T cell exhaustion in the tumor microenvironment

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of RBPJ as drug target in preparation of drug for inhibiting T cell depletion
  • Application of RBPJ as drug target in preparation of drug for inhibiting T cell depletion
  • Application of RBPJ as drug target in preparation of drug for inhibiting T cell depletion

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1 Acquisition of clinical samples of colorectal cancer and single-cell library construction and sequencing

[0053] The colorectal cancer samples with polyps in the clinical surgical resection were selected, the patients had not received any treatment, and the tumor had no distant metastasis. A total of 11 tissue samples from 3 colorectal cancer patients with colorectal polyps were collected, including peripheral blood, normal intestinal tissue, polyps, and tumor tissue, for single-cell sequencing (see figure 1 ). figure 1 In , the boxed part of P1 and P3 represents Normal, Cancer and Polyp from left to right; the boxed part of P2 represents Para-cancer, Normal, Cancer and Polyp from left to right.

[0054] Various tissues were collected according to the following standards: Tumor tissues were collected in different ways according to the designated direction, the right 1 / 3 of polyp tissues were collected, intestinal tissues within 2 cm from the tumor were regar...

Embodiment 2

[0057] Embodiment 2 bioinformatics analysis

[0058] 1. Single-cell transcriptome sequencing data preprocessing

[0059] For the original sequencing fragments, we used Cell Ranger to compare them to the GRCh38 reference genome to obtain a gene expression matrix, and a total of 54,788 cells were detected. In order to correct the phenomenon of gene omission in single-cell sequencing, we used the scimpute R software package. During the use, except for setting the parameter k=15, other default parameters were used.

[0060] Subsequent data quality control was performed using the Seurat R software package. Genes were first filtered to exclude genes expressed in fewer than three cells, and cells were then filtered to exclude cells expressing fewer than 200 genes or with mitochondrial gene content greater than 25% of the total UMI count. After data filtering, 44,178 cells remained. Since the sequencing depth of different samples is not the same, it is necessary to normalize the da...

Embodiment 3

[0073] Embodiment 3 Design the inhibitor of RBPJ

[0074] As of September 2020, a total of nine crystal structures of RBPJ have been recorded in the RCSB Protein Data Bank (www.rcsb.org). Table 1 lists specific information about these structures, which were all obtained by X-ray diffraction. Four of them are of human origin, and the ligands that bind to RBPJ are mainly nucleic acids and other transcription factors, as well as small molecules that help stabilize protein structures.

[0075] Table 1 Currently available bioinformatics data for RBPJ structures

[0076]

[0077] The four human RBPJ crystal structures (PDBID: 6PY8, 3NBN, 3V79 and 2F8X) were overlaid, see Figure 5 Column 1 of the table; it is found that the difference in their RMSD values ​​is less than ,See Figure 5 Column 2 of the table, indicating that the conformations are basically similar. Therefore, the 6PY8 crystal structure with the most complete structure was selected for subsequent analysis. F...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses an application of RBPJ as a drug target in preparation of a drug for inhibiting T cell depletion. The RBPJ can be used as a drug target for preparing a drug for inhibiting T cell depletion; the invention discloses a T cell depletion inhibitor. The inhibitor is an inhibitor for inhibiting the expression quantity of RBPJ. According to the invention, the RBPJ gene capable of being used as a target for preparing the medicine for inhibiting T cell depletion is obtained through screening, and the inhibitor capable of inhibiting the gene expression is designed and synthesized,so that the T cell depletion is effectively inhibited, and the tumor immunotherapy effect is enhanced.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to the application of RBPJ as a drug target in the preparation of drugs for inhibiting T cell exhaustion. Background technique [0002] Malignant tumor is one of the most important diseases that endanger human health, and there is still no effective treatment. Previous studies focused on the treatment of tumor cells, but the evolution and mutation of tumor cells lead to resistance to therapeutic drugs, causing tumor recurrence and metastasis. In recent years, more and more studies have begun to focus on the tumor microenvironment. Treatments targeting the tumor microenvironment can effectively prevent tumor growth, such as enhancing the killing effect of infiltrating T cells and inhibiting tumor-associated fibroblasts and macrophages. [0003] T cells are a crucial cell type in the tumor microenvironment and play an important role in anti-tumor immunity. In recent year...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K45/06A61K31/08A61K31/137A61K31/16A61K39/395A61P35/00C12N5/0783C12Q1/6886G16B15/30G16B30/00G16B40/00
CPCA61K45/00A61K45/06A61K31/16A61K31/08A61K31/137A61K39/3955A61P35/00C12N5/0636C12Q1/6886G16B15/30G16B30/00G16B40/00C12Q2600/158A61K2039/505A61K2300/00
Inventor 郑晓博
Owner WEST CHINA HOSPITAL SICHUAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap