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A kind of nucleic acid and its application and pharmaceutical composition

A composition and nucleic acid technology, applied in the direction of introducing foreign genetic material, medical formula, genetic material components, etc. by using a carrier, which can solve problems such as poor effect

Active Publication Date: 2015-09-16
KUNSHAN RNAI INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to overcome the defect that the current nucleic acid interference drug has a poor effect of interfering with HBV in vivo, and provide a nucleic acid interference drug with a better effect of interfering with HBV in vivo

Method used

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  • A kind of nucleic acid and its application and pharmaceutical composition
  • A kind of nucleic acid and its application and pharmaceutical composition
  • A kind of nucleic acid and its application and pharmaceutical composition

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Experimental program
Comparison scheme
Effect test

Embodiment approach

[0036] According to a particularly preferred embodiment of the present invention, the nucleic acid contains siRNA(m)-8 whose sense strand sequence is SEQ ID NO: 78 and antisense strand sequence is SEQ ID NO: 79, and the sense strand sequence is SEQ ID NO: 80 And the antisense strand sequence is siRNA(m)-23 of SEQ ID NO:81, the sense strand sequence is SEQ ID NO:82 and the antisense strand sequence is siRNA(m)-27 and the sense strand sequence of SEQ ID NO:83 It is SEQ ID NO: 84 and the antisense strand sequence is siRNA(m)-30 of SEQ ID NO: 85, the sense strand sequence is SEQ ID NO: 86 and the antisense strand sequence is siRNA (m) of SEQ ID NO: 87 -32 and at least one of siRNA(m)-34 whose sense strand sequence is SEQ ID NO: 88 and antisense strand sequence is SEQ ID NO: 89.

[0037] According to the nucleic acid of the present invention, wherein the siRNA comprising the siRNA-8, the siRNA-23, the siRNA-27, the siRNA-30, the siRNA-32 and the siRNA-34 can be passed Obtained by ...

preparation Embodiment 1

[0052] The siRNAs listed in Table 1 were chemically synthesized by Shanghai GenePharma Company.

[0053] Table 1

[0054]

[0055]

[0056] After sequence comparison, there is no homologous sequence with a length of more than 16 bases between the sequence of the above siRNA and the genome sequence of human or mouse. Moreover, the above siRNA is formed by annealing equimolar sense strand and antisense strand.

preparation Embodiment 2

[0058] Entrust Shanghai GenePharma Company to prepare plasmids expressing shRNA listed in Table 2. The plasmid expressing shRNA is recorded as shRNA(p), which are shRNA(p)-8, shRNA(p)-23, shRNA(p)-27, shRNA(p)-30, shRNA(p)-32, shRNA( p)-34, shRNA(p)-4, shRNA(p)-9, shRNA(p)-17, shRNA(p)-22, shRNA(p)-26, shRNA(p)-35, shRNA(p) )-36, shRNA(p)-37, shRNA(p)-38, shRNA(p)-40 and shRNA(p)-45. Among them, all plasmids expressing shRNA are inserted into the empty vector numbered pGenesil-1 purchased from Wuhan Jingsai Company (the sequence of the empty vector is as shown in its instruction manual), and a positive-sense short reverse sequence corresponding to the positive-sense strand of siRNA is inserted. A nucleic acid fragment encoding shRNA composed of a repeat fragment, a loop fragment (SEQ ID NO: 25, namely 5'-TCAAGAGA-3') and an antisense short inverted repeat fragment corresponding to the antisense strand of siRNA concatenated.

[0059] Table 2

[0060]

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PUM

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Abstract

The invention provides a nucleic acid which is siRNA or plasmid with inserted nucleic acid fragment coding short-hairpin ribonucleic acid. The invention also provides an application of the nucleic acid in preparing a medicine composition used for preventing and / or treating hepatitis B. The invention also provides a medicine composition comprising the nucleic acid and pharmaceutically acceptable carriers. With the nucleic acid and the medicine composition provided by the invention, an in-vivo HBV interference effect with an inhibition rate higher than 30% can be achieved.

Description

technical field [0001] The present invention relates to the field of biopharmaceuticals, in particular to a nucleic acid, the application of the nucleic acid and a pharmaceutical composition. Background technique [0002] Hepatitis B (hepatitis B) is an infectious disease caused by hepatitis B virus (HBV). Hepatitis B is mainly transmitted through blood and body fluids, and the clinical manifestations are diverse, including acute, chronic, cholestatic and severe hepatitis, and it is easy to develop into chronic hepatitis and cirrhosis, and a few cases can also be transformed into primary hepatocellular carcinoma . [0003] At present, HBV infection is a worldwide epidemic, mainly affecting children and young adults. According to the report of the World Health Organization, about 400 million people in the world are chronic HBV carriers, and about 1 million people die every year from liver failure, cirrhosis and primary hepatocellular carcinoma caused by HBV infection. Chin...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/113C12N15/63A61K48/00A61P31/20
Inventor 梁子才李德毓周春雷王茜
Owner KUNSHAN RNAI INST