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Small interfering nucleic acid, composition and application

A nucleotide and nucleotide sequence technology, applied in the field of biomedicine, can solve the problem of lack of effective antiviral drugs for SARS-CoV-2 virus, and achieve the effect of great clinical significance and promotion value

Active Publication Date: 2020-05-12
SUZHOU GENEPHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Scientists and clinicians around the world are working rapidly to combat the respiratory disease COVID-19 caused by the new coronavirus, but there is still a lack of effective antiviral drugs against the SARS-CoV-2 virus, and the current treatment is isolation treatment and symptomatic support treatment-based

Method used

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  • Small interfering nucleic acid, composition and application
  • Small interfering nucleic acid, composition and application
  • Small interfering nucleic acid, composition and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] Synthesis of small interfering nucleic acids

[0071] The novel coronavirus (SARS-CoV-2) genome (Genebank accession number; MN908947.3) (SEQ ID NO: 1) with a relatively conserved sequence was selected as the template. A 21bp nucleotide sequence was selected for the conserved region of the SARS-CoV-2 gene, and a small interfering nucleic acid (siRNA) was designed.

[0072] The siRNA designed in this example was synthesized by Shanghai Gemma Pharmaceutical Technology Co., Ltd., and the sequence of the synthesized siRNA is shown in Table 1.

[0073] Table 1

[0074]

[0075]

[0076]

[0077] As shown in Table 1, this embodiment also sets the siRNA with the nucleotide sequence of the sense strand as shown in SEQ ID NO: 102 and the nucleotide sequence of the antisense strand as shown in SEQ ID NO: 103, and the number is M-siNC It is an irrelevant sequence that has no corresponding target site with the new coronavirus (SARS-CoV-2) gene, and serves as a negative co...

Embodiment 2

[0079] Synthesis of Modified Small Interfering Nucleic Acids

[0080] The modified siRNA shown in Table 2 is obtained by chemically modifying the sense strand of the sequence in Table 1, that is, the nucleotide residues of the 1st, 2nd, 3rd, 19th, 20th, and 21st bases of the sense strand The 2' hydroxyl groups of the pentose group are all modified by methoxy groups, and the phosphate groups between the 1st, 2nd, and 3rd bases of the sense chain are phosphorothioate groups, and the 19th, 20th, and 3rd bases of the sense chain are The phosphate group between the 21 bases is a phosphorothioate group; the antisense strand is not modified, and the siRNA designed in this example is synthesized by Shanghai Gemma Pharmaceutical Technology Co., Ltd., and the sense strand of the siRNA is synthesized at 5 'Terminal link cholesterol for modification.

[0081] Table 2

[0082]

[0083]

[0084]

[0085] Among them, m represents that the pentose group in the nucleotide residue on...

Embodiment 3

[0087] Dual luciferase reporter gene plasmid construction

[0088] The dual-luciferase reporter gene plasmid GP-miRGLO vector used in this example (the sequence of the empty vector is shown in its instruction manual) was purchased from Promega (product number E1330), and the map information is as follows: figure 1 shown. Insert a novel coronavirus (SARS-CoV-2) genome sequence into the GP-miRGLO vector to prepare the dual luciferase reporter gene plasmid shown in Table 3.

[0089] table 3

[0090]

[0091]

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PUM

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Abstract

The invention discloses small interfering nucleic acid as well as a composition and application thereof. The invention claims to protect siRNA, which is PP-1758, PP-17660, PP-20091, PP-20163, SP-26, SP-179, SP-2013, SP-2867, SP-3169, SP-3552, MG-83, NP-208 or NP-241, wherein a part of nucleotides of the positive-sense strand are 2 '-O-methyl ribonucleotides, and a part of phosphate groups are thiophosphate groups. The invention provides brand new siRNA and a composition thereof. The brand new siRNA and the composition thereof can effectively prevent and / or treatment novel coronavirus.

Description

technical field [0001] The present invention relates to the field of biomedical technology, in particular to a small interfering nucleic acid that inhibits gene expression of a novel coronavirus and the application of the small interfering nucleic acid in the preparation of a pharmaceutical composition for preventing and / or treating novel coronavirus pneumonia. Background technique [0002] In late 2019 and early 2020, a new type of coronavirus pneumonia (CoronaVirusDisease2019, COVID-19) broke out in Wuhan, China. COVID-19 is an acute infectious pneumonia, and researchers have found that its pathogen is caused by a novel betacoronavirus not previously found in humans, which was subsequently named SARS-CoV by the World Health Organization (WHO)- 2. The initial symptoms of COVID-19 patients are mostly fever, fatigue and dry cough, and gradually develop severe symptoms such as dyspnea. The prognosis of most patients is good, and acute respiratory distress syndrome, septic sh...

Claims

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Application Information

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IPC IPC(8): C12N15/113A61K48/00A61K31/713A61P31/14A61P11/00
CPCC12N15/1131A61P31/14A61P11/00A61K31/713C12N2310/141C12N2310/315C12N2310/321
Inventor 胡荣宽董长贵张佩琢张紫楠李琴汪昕杜永华杜宏
Owner SUZHOU GENEPHARMA
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