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Nucleic acid for inhibiting Ebola virus, pharmaceutical composition containing nucleic acid, and use of nucleic acid and pharmaceutical composition

An Ebola virus and nucleotide technology, applied in the field of siRNA, can solve the problem of lack of sufficient understanding of the siRNA degradation process

Active Publication Date: 2020-07-07
SUZHOU RIBO LIFE SCIENCE CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, those skilled in the art have done a lot of research on siRNA. However, the degradation process and mechanism of siRNA in blood are still insufficiently understood. Experiment to verify the process

Method used

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  • Nucleic acid for inhibiting Ebola virus, pharmaceutical composition containing nucleic acid, and use of nucleic acid and pharmaceutical composition
  • Nucleic acid for inhibiting Ebola virus, pharmaceutical composition containing nucleic acid, and use of nucleic acid and pharmaceutical composition
  • Nucleic acid for inhibiting Ebola virus, pharmaceutical composition containing nucleic acid, and use of nucleic acid and pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0270] Preparation Example 1 This example illustrates the preparation of siRNA provided by the present disclosure and control siRNA

[0271] In this preparation example, the siRNA sequences in Table 1 were synthesized. Among them, Examples 1-10 are modified siRNAs specifically targeting Ebola virus of the present disclosure, wherein siP1S, siP2S, siP5S, siP6S, siP7S and siP10S target EBOVVP35mRNA, and siP3S, siP4S, siP8S and siP9S target EBOV L mRNA; Comparative Examples 1-5 are unmodified siRNA naked sequences; Comparative Example 6 is a negative control siRNA that has no inhibitory effect on Ebola virus genes.

[0272] In this preparation example, the siRNAs listed in Table 1 below were obtained by the conventional solid-phase phosphoramidite method. Use DEPC water (purchased from Amresco, product number E174) to dissolve equimolar sense strand and antisense strand respectively, heat to 70-95°C, and then cool at room temperature. After this annealing process, the two single...

preparation example 2

[0278] Preparation Example 2 This example illustrates the preparation of siRNA compositions

[0279]The first siRNA and the second siRNA were mixed in equimolar amounts to obtain an siRNA composition; the types of the first siRNA and the second siRNA used are shown in Table 2.

[0280] The kind of the first siRNA and the second siRNA used in the siRNA composition of table 2

[0281] siRNA composition first siRNA Second siRNA C1 siP6S siP9S C2 siP7 siP9S

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Abstract

The invention discloses a siRNA that inhibits Ebola virus gene expression. The siRNA contains a sense strand and an anti-sense strand, wherein the sense strand includes a nucleotide sequence 1, the anti-sense strand includes a nucleotide sequence 2, and the nucleotide sequence 1 and the nucleotide sequence 2 are at least partially reversely complementary to form a double-stranded region. The lengths of the nucleotide sequence 1 and the nucleotide sequence 2 are both 19 nucleotides, and the nucleotide sequence 2 is at least partially reversely complementary to a first nucleotide sequence, wherein the first nucleotide sequence is a nucleotide sequence with the same length as the nucleotide sequence 2 in Ebola virus mRNA. According to the direction from the 5' end to the 3' end, nucleotides at 7th, 8th, and 9th positions of the nucleotide sequence 1 are fluoro-modified nucleotides, and nucleotides at 2nd, 6th, 14th, and 16th positions of the nucleotide sequence 2 are fluoro-modified nucleotides. The siRNA and a pharmaceutical composition containing the siRNA have good activity to inhibit Ebola virus gene expression.

Description

technical field [0001] The present disclosure relates to a siRNA, a pharmaceutical composition containing the siRNA and their uses. Specifically, the present disclosure relates to an siRNA for inhibiting Ebola virus gene expression, a pharmaceutical composition containing the siRNA as an active ingredient, and the siRNA and the pharmaceutical composition are used for preventing and / or treating Ebola virus. Drug use for Bora virus disease. Background technique [0002] Ebola virus disease is an acute hemorrhagic infectious disease caused by Ebola virus (EBOV) belonging to the filoviridae family. It is mainly transmitted through the blood and excrement of the patient. The main clinical manifestations are acute onset fever, myalgia, bleeding rash, and liver and kidney dysfunction. [0003] EBOV belongs to the filovirus family Filoviridae, which is a negative-strand RNA virus with a single strand without segments; it is divided into four subtypes: Zaire Ebola Virus (Zaire Ebol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113A61K31/713A61P31/14
CPCC12N15/1131A61P31/14C12N2310/14
Inventor 张鸿雁高山康代武刘涛
Owner SUZHOU RIBO LIFE SCIENCE CO LTD