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Application of SUMF2 gene in preparation of medicine for preventing and/or treating allergic asthma attack and reducing airway hyperresponsiveness

An allergic asthma, genetic technology, applied in the biomedical field, can solve problems such as airflow limitation

Inactive Publication Date: 2021-09-14
HARBIN INST OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although treatment can delay asthma disease progression, inflammation-induced airway remodeling is irreversible and ultimately causes irreversible airflow limitation

Method used

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  • Application of SUMF2 gene in preparation of medicine for preventing and/or treating allergic asthma attack and reducing airway hyperresponsiveness
  • Application of SUMF2 gene in preparation of medicine for preventing and/or treating allergic asthma attack and reducing airway hyperresponsiveness
  • Application of SUMF2 gene in preparation of medicine for preventing and/or treating allergic asthma attack and reducing airway hyperresponsiveness

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] A screening method for the SUMF2 gene in patients with allergic asthma, using bioinformatics analysis to establish an asthma time-series model, the analysis process is as follows figure 1 Shown in a.

[0033] Obfuscation of RNA-seq and microarray data of nasal mucosa and airway epithelium in patients with asthma. First, the GSVA analysis method was used to reduce the dimensionality of the original data, so that the expression profile data changed from the expression value of a single gene to the enrichment degree of different signaling pathways, and a cell pathway enrichment matrix was obtained. Secondly, weighted gene co-expression network analysis (WCGNA) was performed on 5 sets of RNA-seq and microarray data from different samples, using genes as nodes and the Pearson correlation of expression values ​​between genes as weights to generate a gene expression regulation network map. Select the common parts of the 5 sets of gene expression regulatory network diagrams to...

Embodiment 2

[0039] Allergic asthma animal model construction method and index detection

[0040] The 4-week-old C57BL / 6N female mice of SPF grade were fed with normal feed, free to drink water, and grew normally in a well-ventilated environment with a temperature of 20-25°C and a humidity of 40%-60%. The feeding and use of experimental animals adopts the "3R" principle and gives humanitarian care.

[0041] The mice were randomly divided into acute asthma group, acute exacerbated asthma group, chronic asthma group, chronic asthma rest group for 2 weeks, chronic asthma rest group for 3 weeks, chronic asthma relapse group for 4 weeks, acute lung injury group and controls in each group Group. After the experiment, the mice were euthanized, and the success of the model establishment was judged according to the pathological characteristics of the lungs, such as smooth muscle hyperplasia, pulmonary fibrosis, and the number of infiltration of eosinophils, neutrophils, lymphocytes, and monocytes....

Embodiment 3

[0047] Packing, collection, purification and titer determination of adeno-associated virus

[0048] The adeno-associated virus subtypes (AAV5, AAV6, AAV9) that have been reported in the literature and can bind to mouse lung cells were selected for preliminary experiments. The mice were lavaged with AAV5-GFP, AAV6-GFP, and AAV9-GFP viruses provided by Hanheng Company, and euthanized 21 days later, and the expression of GFP in mouse lung cells was detected by immunohistochemical staining . Such as Figure 5 As shown in c, AAV5 mainly binds to alveolar epithelial cells; AAV9 can bind to both airway epithelial cells and alveolar epithelial cells; and AAV6 can well target airway epithelial cells. Therefore, AAV6 was chosen as the vector to deliver the Sumf2 gene.

[0049] In this example, AAV6 subtypes that can well target mouse lung airway epithelial cells were selected to overexpress SUMF2. The AAV6 genome includes two inverted terminal repeats (ITRs) and two open reading fra...

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Abstract

The invention provides application of an SUMF2 gene in preparation of a medicine for preventing allergic asthma attack and reducing airway hyperresponsiveness and belongs to the technical field of biomedicine. According to the application, a bioinformatics technology and an animal experiment verify that abnormality of a metabolic pathway of an SUMF1 / 2-glycosaminoglycan enables epithelial cells to generate an immune-memory-similar phenomenon, and a TH2 reaction can be promoted when the SUMF1 / 2-glycosaminoglycan is in contact with allergens again. According to the application, 20 days before asthma is induced, an adeno-associated virus vector is utilized to over-express the SUMF2 gene derived from epithelial cells of an airway of a mouse, and compared with a control group, the airway inflammatory response of lungs of asthmatic mice can be obviously improved. Therefore, the overexpressed SUMF2 can be used as a genetherapy target for preventing allergic asthma and reducing the airway hyperresponsiveness. Therefore, the use of the adeno-associated virus for overexpression of the SUMF2 in the field of prevention of the allergic asthma has a wide application value and a broad market prospect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of SUMF2 gene in the preparation of medicines for preventing and / or treating allergic asthma attack and reducing airway hyperresponse. Background technique [0002] Allergic asthma is a special type of bronchial asthma. At present, the treatment of allergic asthma is mainly based on bronchodilators, leukotriene receptor antagonists and hormone drugs. Severe grade 3 or above asthma requires the addition of long-acting cholinergic receptor antagonists, anti-IgE, anti-IL-5 or anti-IL-4R for treatment. These drugs are mainly used to reduce airway inflammatory response and relieve smooth muscle spasm after the onset of asthma, but have limited effect on airway remodeling caused by inflammatory injury. Although treatment can delay asthma disease progression, inflammation-induced airway remodeling is irreversible and ultimately causes irreversible airflo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K38/17A61P11/06A61P37/08
CPCA61K48/005A61K48/0008A61K38/1709A61P11/06A61P37/08C12N15/86C12N2750/14143A61K48/0075
Inventor 姜蒙姜晓峰高会军李宾孙文轩郑晔佟明斯
Owner HARBIN INST OF TECH
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