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Targeted fusion protein against HBV replication and construction method thereof

A technology of fusion protein and construction method, applied in the field of targeted fusion protein, can solve the problems of side effects, treatment failure, easy to produce tolerance and so on

Active Publication Date: 2021-04-20
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Claims
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Problems solved by technology

However, the drug is prone to tolerance and many side effects, which make the treatment fail

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  • Targeted fusion protein against HBV replication and construction method thereof
  • Targeted fusion protein against HBV replication and construction method thereof
  • Targeted fusion protein against HBV replication and construction method thereof

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Embodiment Construction

[0049] The present invention will be described in detail below in combination with specific embodiments.

[0050] In order to enhance the effect of A3A and UNG2 on degrading cccDNA, the present invention localizes A3A and UNG2 to the nucleus and specifically binds to the characteristics of cccDNA, and uses HBV core protein (HBc) as the targeting molecule of A3A and UNG2 to guide A3A and UNG2 into the nucleus and interact with it. Combined with cccDNA, play the role of degrading cccDNA. HBc is a structural protein that assembles the viral nucleocapsid, and has the characteristic of specifically binding to HBV cccDNA, and the region that determines this characteristic is the C-terminal region (CTD) of HBc, and this region also has the function of nuclear localization.

[0051] HBc is the core protein of HBV, which is a structural protein for assembling the viral nucleocapsid. HBc is 183aa long and is divided into two parts: N-terminal region (1-143aa) and C-terminal region (CTD...

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Abstract

The invention relates to an anti-HBV replication targeting fusion protein and a construction method thereof. Utilizing the characteristic that the C-terminal region (CTD) of the hepatitis B virus core protein HBc can specifically bind to HBV cccDNA, this peptide is used as a guide molecule targeting cccDNA, which is denoted as HBc144; A3A‑HBc144 coding gene sequence and HBc144 were synthesized ‑UNG2 coding gene sequence, and clone these two segments into the multiple cloning sites MCS1 and MCS2 of the eukaryotic expression vector pVITRO2‑neo‑mcs to construct a recombinant double expression vector Pvitro2‑A3A‑HBc / HBc‑UNG2, The recombinant vector can simultaneously express two fusion proteins in hepatocytes, that is, A3A-HBc144 and HBc144-UNG2. The present invention realizes the targeting of A3A and UNG2 to HBV cccDNA, which is more effective than the vector expressing A3A or A3A-HBc alone. Strong inhibitory effect on virus replication.

Description

technical field [0001] The invention relates to a targeting fusion protein, in particular to a targeting fusion protein against HBV replication and a construction method thereof. Background technique [0002] Hepatitis B virus (HBV) infection is the main cause of hepatitis B, liver cirrhosis and liver cancer. There are about 350 million HBV-infected people in the world, and there are about 130 million people in China, including about 30 million patients with chronic hepatitis B. Chronic HBV infection is difficult to cure because it is difficult to completely remove HBV cccDNA in the nucleus of infected cells, and HBV cccDNA is the core substance of virus replication. Therefore, it is an important goal of anti-HBV research to find an effective method to remove cccDNA. [0003] Recent studies have found that interferon α (IFNα) can not only inhibit virus replication from multiple steps in the HBV life cycle, but more importantly, induce specific cccDNA degradation. However,...

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Application Information

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IPC IPC(8): C07K19/00C12N15/62C12N15/85C12N15/64A61K38/50A61K38/47A61K47/64A61P31/20
CPCA61K38/00C07K2319/09C12N9/2497C12N9/78C12N15/64C12N15/85C12N2800/107C12Y302/02027C12Y305/04001
Inventor 郭晏海成珊曹丽妍杜娟
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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