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Composition for inhibiting replication of hepatitis b virus

A technology of hepatitis B virus and composition, which can be applied to antiviral agents, medical preparations containing active ingredients, genetic material components, etc., and can solve problems such as microRNAs that have not yet been discovered

Pending Publication Date: 2021-06-25
TOKYO METROPOLITAN INST OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It has been reported that HBV-derived mRNA is the target of host microRNA, and its expression is inhibited ( figure 2 , Non-Patent Document 2: Zhang GL et al., Antiviral Res 94, 169-175 (2012)) However, no microRNA that directly promotes HBV replication has been found

Method used

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  • Composition for inhibiting replication of hepatitis b virus
  • Composition for inhibiting replication of hepatitis b virus
  • Composition for inhibiting replication of hepatitis b virus

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Experimental program
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Effect test

Embodiment 1

[0076] 1. Method

[0077]The present inventors used humanized liver chimeric mice as an animal model of HBV infection. HBV of the AeJPN strain (AB246338.1) of genotype A and HBV of the CJPNAT strain of genotype C (AB246345.1) were used as infection sources. RNA was prepared from mouse livers 10 weeks after infection for RNA-seq analysis. PXB cells from PhoenixBio were used as primary human hepatocytes. Dharmacon's miRIDIAN microRNA mimics were used as microRNAs, and Exiqon's miRCURY LNA microRNA Power Inhibitors (YI04104482) were used as microRNA inhibitors. The multifunctional envelope-type nanodevice (MEND) was used to deliver microRNA to primary human hepatocytes (Yamamoto N, Sato Y, Munakata T, Kakuni M, Tateno C, Sanada T, Hirata Y, Murakami S, Tanaka Y, Chayama K, Hatakeyama H , Hyodo M, Harashima H, Kohara M.JHepatol.2016Mar; 64(3):547-55.Novel pH-sensitive multifunctional envelope-type nanonode device for siRNA-based d treatments for chronic HBV infection.), in the ...

Embodiment 2

[0109] About the mechanism

[0110] Since miR-4453 was found to target the 5'ε of pgRNA, the present inventors analyzed the behavior of the 3.5 kb pgRNA by Northern blot. It was found that in HepG2.2.15 cells where HBV was constitutively replicating, the amount of pgRNA increased when miR-4453 was added, and the amount of pgRNA decreased when miR-4453 inhibitor was added. In addition, we analyzed the stability of pgRNA by Northern blotting in the state where actinomycin D was added to the culture system to stop the synthesis of new RNA. It was found that the stability of pgRNA increased with miR-4453 ( Figure 9 ).

[0111] Regarding the effect of different miR-4453 inhibitors

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Abstract

Provided is a medicinal composition for treating hepatitis B. The present invention provides: a composition for inhibiting the replication of the hepatitis B virus, the composition comprising an inhibitor of a micro RNA that binds to an epsilon signal sequence in the 5'-side of a pregenomic RNA of the hepatitis B virus; and a medicinal composition for treating a hepatitis B virus infection.

Description

technical field [0001] The present invention relates to compositions for inhibiting the replication of hepatitis B virus. Background technique [0002] microRNA (miRNA) is a short RNA that does not encode a protein and is about 22 bases in length. It is a factor that forms a complex with the AGO protein and mainly regulates gene expression by degrading and repressing translation of mRNA with a target sequence ( figure 1 ). Standard microRNA production process such as figure 1 As shown, primary microRNA (pri-microRNA), which is a primary transcript containing a hairpin structure, is synthesized by transcription. Drosha, which acts as RNaseIII in the nucleus, cleaves the hairpin base of pri-microRNA to form a microRNA precursor (pre-microRNA). The resulting pre-microRNA is mainly transported from the nucleus to the cytoplasm through the export protein 5 (Exportin-5), and then cut by another Dicer as RNaseIII to form a 20-24 base double-stranded RNA (microRNA duplex). The d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7105A61K31/7115A61K31/713A61K45/00A61K48/00A61P31/20
CPCA61P31/20A61K31/713A01K2227/105A01K2267/0337C12N15/113
Inventor 栋方翼小原道法真田崇弘
Owner TOKYO METROPOLITAN INST OF MEDICAL SCI