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Active molecule capable of suppressing gene replication of Ebola virus and usage method thereof

A technology of Ebola virus and active molecules, applied in the field of siRNA inhibitors, can solve the problem that vaccines cannot produce strong immune responses

Inactive Publication Date: 2015-11-18
SIRNAOMICS BIOPHARMACEUTICALS (SUZHOU) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In particular, siRNA therapy may benefit specific patient populations, such as infants or the elderly who do not mount a strong immune response to the vaccine and are not fully protected by the vaccine
[0027] 5. siRNA Therapeutic Development - Challenges Facing SRS and RSS
[0030] 6. The development of siRNA therapy - the challenge of introducing barriers

Method used

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  • Active molecule capable of suppressing gene replication of Ebola virus and usage method thereof
  • Active molecule capable of suppressing gene replication of Ebola virus and usage method thereof
  • Active molecule capable of suppressing gene replication of Ebola virus and usage method thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0070] Example 1. Screening of siRNA cocktails for the treatment of EVD

[0071] An important concept in designing siRNAs against viral infections is the simultaneous targeting of multiple viral genes using siRNA cocktails containing multiple siRNA oligonucleotides. Given the unique functions of the targeted viral genes in viral proliferation and infection, and their potential to block the RNAi mechanism, we will simultaneously target three viral genes. Cocktail No. 1 (CT01) targets VP24, VP35 and LP proteins; Cocktail No. 2 (CT02) targets VP30, VP35 and LP proteins; Cocktail No. 3 (CT03) targets VP24, VP40 and LP proteins; Cocktail No. 4 (CT04 ) targets VP30, VP40 and LP proteins; Cocktail No. 5 (CT05) targets VP35, VP40 and LP proteins; Cocktail No. 6 (CT06) targets VP24, VP30 and VP35; Cocktail No. 7 (CT07) targets VP30, VP35 and VP40; Cocktail No. 8 (CT08) targets VP24, VP30 and LP proteins.

example 2

[0072] Example 2. Sequence of siRNA cocktail CT01

[0073] CTO1(25) includes: VP24(3):5'-guggaagguuuauugggcugguauu-3', VP35(4):5'-cuucauuggcuacuguugtgcaaca-3', and LP(5):5'-cauuaaguacacaaugcaagaugcu-3'.

[0074] CT01(21) includes: VP24(9):5'-ggacgauacaaucuaauaudtdt-3', VP35(9):5'-gagcagcuaaugaccggaadtdt-3', and LP(9):5'-gaccaaugugaccuugucadtdt-3'.

example 3

[0075] Example 3. Sequence of siRNA cocktail CT02

[0076] CT02(25) includes: VP30(3):5'-ggagaguuuaacugauagggaauua-3'; VP35(4)5'-cuucauuggcuacuguugtgcaaca-3', and LP(5):5'-cauuaaguacacaaugcaagaugcu-3'.

[0077] CT02(21) includes: VP30(9):5'-ucgaggugaguaccgucaadtdt-3', and VP35(9):5'-gagcagcuaaugaccggaadtdt-3', and LP(9):5'-gaccaaugugaccuugucadtdt-3'.

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Abstract

The invention relates to an active molecule capable of suppressing gene replication of Ebola virus. The active molecule is compsoed of nanogranule formulation of HKP or SLiC or RPH vector and siRNA cocktail for preventing and treating Ebola virus infection. The active molecule specificly relates to the siRNA molecule cocktain of targeted Ebola virus, cocktail siRNA composition of targeted Ebola virus gene conservative region, nanoparticle of siRNA cocktail and Histidine-lysine copolymer (HKP), or / and spermine-lipid-cholesterol (SLiC)nanoparticle formulation composition; composition of siRNA cocktail and HKP or SLiC nanoparticle formulation. The formulation is modified by Arg-Gly-Asp(RGD) polypeptide ligands which is specific to a endothelial cell surface acceptor or erythrocyte, and is called RGD-PEG-HKP(RPH) vector system. The invention also relates to a method for testing new siRNA formualtion in cell cultrue, a method for testing new siRNA formulation in guinea pig model and monkey model and a method for testing nanoparticle-containing siRNA formualtion in injection liquid for human.

Description

technical field [0001] The invention relates to an siRNA inhibitor for treating Ebola virus, its nanoparticle carrier and the configuration and method of the drug. Background technique [0002] 1. Ebola virus infection [0003] Ebola virus infection disease (referred to as Ebola disease, EVD) is a serious and fatal disease that occurs in humans and primates, and the mortality rate is often as high as 50%-90%. Since the discovery of Ebola virus in Congo and Sudan in 1976, so far, five subtypes of Ebola virus have been discovered: Zaire Ebola virus (EBOV), Sudan Ebola virus (SUDV), Ebola Virus (TAFV), Reston Ebola Virus (RESTV) and Bundibugyo Ebola Virus (BDBV). Among them, EBOV, SUDV and BDBV have been identified as responsible for the large outbreak of EVD in Africa. [0004] Ebola virus is a single-stranded linear negative-strand RNA virus belonging to Filoviridae. Its genome is about 19kb in length and encodes seven structural proteins, nucleoprotein (NP), polymerase co...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113C12Q1/68A61K48/00A61P31/14
CPCA61K31/713C12Q1/18A61K47/62A61K47/6929A61P31/14A61K49/0008C12N15/1131C12N2310/14C12N2320/31C12Q1/701C12Q2600/136C12Q2600/178
Inventor 徐军蔡以滨陆阳
Owner SIRNAOMICS BIOPHARMACEUTICALS (SUZHOU) CO LTD
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