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A nucleic acid for inhibiting Ebola virus, pharmaceutical composition containing the nucleic acid and use thereof

A technology of Ebola virus and composition, applied in the field of siRNA, can solve the problems of lack of sufficient understanding of the degradation process of siRNA, and achieve the effects of good in vivo safety, high intracellular stability, and high plasma stability

Active Publication Date: 2022-07-26
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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  • A nucleic acid for inhibiting Ebola virus, pharmaceutical composition containing the nucleic acid and use thereof
  • A nucleic acid for inhibiting Ebola virus, pharmaceutical composition containing the nucleic acid and use thereof
  • A nucleic acid for inhibiting Ebola virus, pharmaceutical composition containing the nucleic acid and use thereof

Examples

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preparation example 1

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

[0271] In this preparation example, the siRNA sequences in Table 1 were synthesized. Among them, Examples 1-10 are the disclosed modified siRNAs specifically targeting Ebola virus, wherein siP1S, siP2S, siP5S, siP6S, siP7S and siP10S target EBOVVP35 mRNA, 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 gene.

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

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] Table 2 Kinds of the first siRNA and the second siRNA used in the siRNA composition

[0281] siRNA composition first siRNA second siRNA C1 siP6S siP9S C2 siP7S siP9S

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Abstract

An siRNA for inhibiting Ebola virus gene expression, the siRNA contains a sense strand and an antisense strand, the sense strand comprises nucleotide sequence 1, the antisense strand comprises nucleotide sequence 2, nucleotide sequence 1 and nucleotide sequence 1 Sequence 2 is at least partially reverse complementary to form a double-stranded region. Both nucleotide sequence 1 and nucleotide sequence 2 are 19 nucleotides in length, and nucleotide sequence 2 is at least partially reverse complementary to the first nucleotide sequence, the first nucleotide sequence is a nucleotide sequence with the same length as the nucleotide sequence 2 in Ebola virus mRNA. In the direction from the 5' end to the 3' end, the nucleotides at positions 7, 8, and 9 of nucleotide sequence 1 are fluorine-modified nucleotides; The nucleotide at position 16 is a fluoro-modified nucleotide. The siRNA and the pharmaceutical composition containing the siRNA have good activity of inhibiting Ebola virus gene expression.

Description

technical field [0001] The present disclosure relates to a siRNA, pharmaceutical compositions containing the siRNA, and uses thereof. Specifically, the present disclosure relates to an siRNA for inhibiting the expression of Ebola virus genes, a pharmaceutical composition containing the siRNA as an active ingredient, and the preparation of the siRNA and the pharmaceutical composition for preventing and / or treating Ebola virus. Medications for bola virus disease. Background technique [0002] Ebola virus disease is an acute hemorrhagic infectious disease caused by Ebola virus (EBOV) of the family filoviridae. It is mainly spread through the blood and excrement of patients, and the clinical manifestations are acute onset fever, myalgia, bleeding rash, and liver and kidney function damage. [0003] EBOV belongs to the Filovirus family Filovirus genus, which is a single-stranded unsegmented negative-strand RNA virus; it is divided into four subtypes: Zaire Ebola Virus (ZEBOV), ...

Claims

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Application Information

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Patent Type & Authority Patents(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