Recombinant vector for human hepatitis B virus and application thereof

Abstract

The invention relates to a recombinant vector for the human hepatitis B virus, belonging to the fields of biological medicine and genetic engineering. Compared with a wild human hepatitis B virus, viral genome involved in the invention lacks a part of a spacer region or the whole spacer region of hepatitis B virus polymerase and a part of a core protein and has a ribosome entry site inserted before the initiation codon of the polymerase. The invention also provides a preparation method for the recombinant vector and application of the recombinant vector to gene therapy targeting to the liver or hepatocytes. The recombinant vector for the human hepatitis B virus provided by the invention supports insertion of a plurality of exogenous sequences and gene expression. A recombinant hepatitis B virus does not have genome replication capability, but recombinant hepatitis B virus genome can realize high-efficiency replication under the condition of supply of the core protein, and packages and secretes infectious intact recombinant hepatitis B virus particles under the condition of simultaneous supply of the core protein and surface protein; so it is proved that the recombinant vector for the human hepatitis B virus provided by the invention has good application prospects as a liver-specific gene introduction vector.

Description

technical field [0001] The invention relates to the fields of genetic engineering, gene therapy and biomedicine, in particular to a recombinant human hepatitis B virus vector and its application in specifically targeting the liver or liver cells to introduce foreign genes. Background technique [0002] It has been reported in the literature that liver diseases such as chronic viral hepatitis, liver cirrhosis, liver cancer, liver disease caused by metabolic disorders, toxic liver disease caused by drugs and other reasons, and autoimmune liver disease are common clinical diseases, which are extremely harmful to the health of the body. There is no effective treatment for the disease, and new treatment methods or drugs are urgently needed, and liver or hepatic cell-specific gene therapy has potential application value in this regard. [0003] Studies have shown that congenital or acquired functional gene defects can lead to serious diseases such as hemophilia and insulin-depende...

AI Technical Summary

Problems solved by technology

Even if the foreign sequence inserted into 5c3c does not lead to premature termination of polymerase translation, the insertion of foreign sequence will inevitably lead to the appearance of irrelevant sequences in the spacer of the polymerase, which may still affect the activity of the polymerase and lead to the low replication ability of the recombinant viral vector

Due to the above reasons, the disclosed 5c3c human hepatitis B virus recombinant vector has certain restrictions on the insertable foreign sequences, which affects the implementation and application to a certain extent.

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