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Application of fusion protein in preparation of drug for treating hepatitis C

A fusion protein and hepatitis C technology, applied in the biological field, can solve the problems of side effects, serious drug-resistant drug interactions, etc., achieve the effect of reducing liver cell apoptosis, reducing liver inflammation, and significant curative effect

Active Publication Date: 2020-07-28
SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In 2011, the new standard triple therapy was approved by the US FDA. This therapy added one of two newly approved protease inhibitors to the traditional anti-hepatitis C standard regimen, which increased the cure rate for HCV genotype 1 infection to about 70%, but its side effects, drug resistance and drug-drug interactions are still serious

Method used

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  • Application of fusion protein in preparation of drug for treating hepatitis C
  • Application of fusion protein in preparation of drug for treating hepatitis C

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Experimental program
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Effect test

Embodiment 1

[0030] Embodiment 1: the therapeutic effect of fusion protein in the cell model of infectious HCV

[0031] The fusion protein (code name: AS1505) is expressed in mouse CHO cells, specifically the amino acid sequence shown in SEQ ID NO: 1:

[0032] SSPSEGLCPPGHHISEDGRDCISCKYGQDYSTHWNDLLFCLRCTRCDSGEVELSPCTTTRNTVCQCEEGTFREEDSPEMCRKCRTGCPRGMVKVGDCTPWSDIECVHKEESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ EGNVFSCSVMHEALHNHYTQKSLSLSLGK

[0033] After the FL-JFH1 plasmid was amplified and identified by enzyme digestion, it was amplified and purified in vitro, and then transferred to Huh7.5.1 by electroporation. The transfected Huh7.5.1 was conventionally subcultured, and the HCV titer was measured by fluorescent quantitative PCR, and the HCV titer was plotted Curves over time, HCV (JFH1) supernatants were prepared in large quantitie...

Embodiment 2

[0037] Embodiment 2: the therapeutic effect of fusion protein in HCV infection mouse model

[0038] CD81 and occludin (OCLN) double transgenic mice were used and divided into treatment group and non-treatment group. HCV was injected through the tail vein, and the injection time was controlled at 1-2min. Drug treatment was started for the treatment group one week after infection, and the fusion protein was administered for 3 weeks, administered twice a week, each intraperitoneal injection of 10mg / ml, the dose 10mg / kg, 1 week and 3 weeks after treatment, the serum and liver tissue of mice in treatment group and non-treatment group were collected. qRT-PCR method was used to detect the copy number of HCV RNA in serum and hepatocytes.

[0039] See the test results figure 2 .

[0040] Depend on figure 2 It can be seen that the non-treatment group is the copy number of HCV in the serum and the replication in the liver within three weeks after the HCV-infected mouse model is not...

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Abstract

The invention relates to the technical field of biology, in particular to application of fusion protein in preparation of a drug for treating hepatitis C. An amino acid sequence of the fusion proteinis selected from one of the followings: 1) an amino acid sequence shown in SEQ ID NO: 1; 2) an amino acid sequence with at least 80% identity; and 3) a modified amino acid sequence. Research finds that the fusion protein reduces liver injury caused by the hepatitis C by blocking cell apoptosis pathways to have a function of protecting liver functions. As a novel candidate drug for treating the hepatitis C, the fusion protein has a novel acting mechanism and clear targets, significant therapeutic effects, high safety and great development potentials.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to the application of a fusion protein in the preparation of medicines for treating hepatitis C. Background technique [0002] Hepatitis C is a global infectious disease caused by hepatitis C virus (HCV). The current global infection rate is about 3%, and about 200 million people are infected. my country announced in 2010 that the serum anti-HCV positive rate of the general population was 0.43%. Hepatitis C is mainly transmitted through blood transfusion. 15%-40% of infected patients can disappear within 6 months, and the remaining 60%-85% develop chronic hepatitis C, of ​​which about 20% of chronic hepatitis C patients are chronically infected with HCV after about 20 years Time to develop cirrhosis or even liver failure or HCV-related hepatocellular carcinoma. [0003] Hepatitis C virus infection is a worldwide health problem. It is generally believed that the body's immune respon...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/16A61K47/64A61P31/14A61P1/16C07K19/00C12N15/62
CPCA61K38/16A61K47/42A61P31/14A61P1/16C07K14/70575C07K2319/00Y02A50/30
Inventor 陈有海万晓春陈倩张青梅夏蒙
Owner SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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