CN104940955A - Application of microRNA in flu treatment medicine preparation - Google Patents

Application of microRNA in flu treatment medicine preparation Download PDF

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Publication number
CN104940955A
CN104940955A CN201510425041.XA CN201510425041A CN104940955A CN 104940955 A CN104940955 A CN 104940955A CN 201510425041 A CN201510425041 A CN 201510425041A CN 104940955 A CN104940955 A CN 104940955A
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mir
pharmaceutical composition
influenza
application
microrna
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CN104940955B (en
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李向东
刘原伍
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China Agricultural University
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China Agricultural University
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Abstract

The invention relates to application of miR-23a in flu treatment medicine preparation and a medicine compound with the miR-23a as an active constituent. The medicine compound can be used for inhibiting the flu virus pathogenic process through the miR-23a.

Description

The application of a kind of microRNA in the medicine of preparation treatment influenza
Technical field
The present invention relates to biological technical field, concrete, relate to the application of a kind of microRNA in the medicine of preparation treatment influenza.
Background technology
MicroRNA (tiny RNA) is one section of Microrna by 20-24 base composition, and it extensively exists in plant, animal, microorganism and fractionated viral.MicroRNA effect in vivo is mainly regulated by the translation process of mode to said target mrna of transcribing rear adjustment.Shaping modes difference to some extent in different plant species, in plant, the main and target mRNA complete complementary of microRNA regulates and controls mRNA and translates, and microRNA only needs seed zone sequence and target gene mRNA complementary to match namely likely to regulate and control this gene in animal body in contrast to this.
Influenza A virus (Influenza A) is the RNA viruses of a class serious threat human health, influenza A virus is common flow Influenza Virus, the most easily morph, the hypotype of influenza A virus is then called " bird flu " by people, bird flu (Bird Flu) is a kind of acute infectious disease caused by bird flu virus, the mankind can be infected after viral gene variation, metainfective symptom main manifestations is high heat, cough, watery nasal discharge, myalgia etc., most with serious pneumonia, the multiple organ failures such as the severe patient heart, kidney cause death, and case fatality rate is very high.This disease is propagated by number of ways such as digestive tract, respiratory tract, skin injury and eye conjunctivas, and personnel and vehicle contact are the key factors propagating primary disease.
MiR-23a is positioned on human body No. 19 chromosome, forms a microRNA gene cluster with miR-24 and miR-27a.This microRNA gene cluster has independent promoter sequence, can independently transcribe.The current research for miR-23a has report to think, and it can by growth and the maturation suppressing transcription factor PU.1 suppress bone-marrow-derived lymphocyte.Also evidence shows that miR-23a can targeting SHP2 gene, expresses promote erythrocytic generation by reducing SHP2.C-Myc can combine with the promoter region in miR-23a gene cluster as transcription factor thus suppress this microRNA gene cluster transcribe the function reaching Gene regulation.Such as in tumor cell, c-Myc suppresses the expression of miR-23a to make the rise of its target molecules transglutaminase finally affect cancerous cell metabolism.Except c-Myc signal path, the p65 albumen in NFkb signal path also can be combined the expression suppressing miR-23a in the promoter region in miR-23a gene cluster.Also there are some researches show miR-23a down-regulated expression in the CD8 positive T cell activated in the recent period, and suppress the expression of miR-23a can improve the kill capability of T cell to tumor cell.In human vascular endothelial, miR-23a can reduce the level of Caspase3 by targeting Caspase7 and STK4 thus resist the apoptotic effect caused by TNF α.But the relevant report of influenza virus is not also suppressed at present with miR-23a.
Summary of the invention
The object of the present invention is to provide a kind of pharmaceutical composition containing miRNA suppressing influenza virus, thus provide a kind of effective way for treating influenza virus.
Influenza virus has the strong feature of sudden change ability, and therefore specific targeting is not enough to tackle influenza virus mutant.MicroRNA is that its mode mainly through non-fully coupling of one section of small fragment RNA carrys out regulator gene expression, therefore effectively can avoid the effect of missing the target because virus mutation causes.
The present inventor suppresses in research to find that miR-23a has influenza effect in the process of the Therapeutic Method of influenza virus.
Therefore, the invention provides the application of miR-23a in the medicine of preparation treatment influenza.
Optionally, described application comprises the medicine preparing resisiting influenza virus.
Optionally, described influenza virus is influenza A virus.
Optionally, to comprise miR-23a and pharmaceutically acceptable carrier is composite makes pharmaceutical composition.
Optionally, described pharmaceutical composition take mir-23a as active component.
Optionally, described pharmaceutical composition contains miR-23a and pharmaceutically acceptable carrier.
Optionally, described compositions is also containing other active component treating and/or preventing influenza.
Optionally, described carrier is in vivo-jetPEI.
Pharmaceutical composition provided by the present invention can suppress influenza virus to alleviate the fatality rate of influenza virus by miR-23a, can reduce the negative effect brought by virus mutation.
Accompanying drawing explanation
Fig. 1 is that the agonist of miR-23a and antagonist are on the impact of C57 Mouse Weight.
Fig. 2 is that the agonist of miR-23a and antagonist are on the impact of C57 mouse temperature.
Fig. 3 is that the agonist of miR-23a and antagonist are on the impact of C57 mouse survival rate.
Detailed description of the invention
Below will the present invention is described in detail by detailed description of the invention.
In the present invention, term " miR-23a " refers to and comprises the RNA sequence of miR-23a or the Microrna of its homologous sequence.The miR-23a in known various source in this area, such as, people, Mus, rabbit etc., these homologous sequences are all included in term miR-23a of the present invention.Also comprise above-mentioned naturally occurring miR-23a sequence in term of the present invention and be substituted, lack or add one or several nucleotide, or still there is the bioactive derivative RNA of miR-23a after chemical modification biology.In the present invention, synthetic and the miR-23a analogies with miR-23a biologic activity that can obtain by buying commercial goods mode also belong to protection scope of the present invention.Such as, the sequence of a kind of miR-23a analogies miR-23aagomir well known in the art (lucky agate gene, catalog number (Cat.No.): B06001): AUCACAUUGCCAGGGAUUUCCAAAUCCCUGGCAAUGUGAUUU as shown in SEQ ID No.1
In addition, miR-23a of the present invention also can be precursor forms, and miR-23a precursor refers in the cell being applied object or can be formed to the precursor of miR-23a in body.The method obtaining naturally occurring miR-23a precursor is conventionally known to one of skill in the art.
As well known to those skilled in the art, the encoding gene of miR-23a is positioned on human body No. 19 chromosome, forms a microRNA gene cluster with miR-24 and miR-27a.Its initial transcription product, after a series of processing, forms ripe miR-23a.MiR-23a precursor only just has corresponding biological function after being processed into ripe miR-23a.
Compositions provided by the present invention may be used for preventing and/or treating influenza infection and the related symptoms that caused by influenza infection and disease.MiR-23a of the present invention containing effective dose in described compositions.
In the present invention, described medicine acceptable carrier comprises various excipient, diluent and adjuvant.Carrier itself is not necessary active component, and does not have undue toxicity after using.This kind of carrier includes but not limited to: normal saline, buffer, glucose, water, glycerol, ethanol etc.
In one embodiment of the invention, described carrier is the mixed proportion scope of in vivo-jetPEI, miR-23a and this carrier is 1 μ g:0.15-0.2 μ l, and preferred ratio is 1 μ g:0.2 μ l.
In one embodiment of the invention, the form of described compositions is suitable for: direct naked RNA injection, liposome RNA direct injection, breeding unsoundness antibacterial carries plasmid DNA method or replication defective adenoviral carries target DNA method etc.
The effective dose of miR-23a of the present invention can adjust accordingly with the order of severity etc. of the pattern of administration and disease to be treated.The selection of preferred effective dose can be comprehensive each because usually determining by those of ordinary skill in the art.Described factor includes but not limited to: the pharmacokinetic parameter of miR-23a, the health status, body weight, route of administration etc. of patient that are treated.
In one embodiment of the invention, the main dosage form of this pharmaceutical composition is isotonic D/W, roughly in the administration of disease progression mid-term stage, within every two days, is administered once, and each administration is carried out according to miR-23a nucleic acid 38-42 μ g.
In the present invention, the route of administration of described pharmaceutical composition is intravenous, via arterial infusion or local injection etc., and medicine-feeding technology well-known to those skilled in the art also can be adopted to carry out administration.
Pharmaceutical composition of the present invention can be combined with other treatment means, for the prevention and therapy of influenza virus.
Embodiment 1
(1) experiment material: C57 mice used is purchased from Beijing Vital River Experimental Animals Technology Co., Ltd.; MiR-23a agonist (miR-23a agomir, catalog number (Cat.No.): B06001) and antagonist (miR-23a antagomir, catalog number (Cat.No.): B05001) are all purchased from lucky agate gene.
(2) totally 3 groups of experiments, often organize 10 mices and inject agomir and antagomir respectively at first 1 day of viral infection influenza virus A/WSN/33 (H1N1) and after infecting the 1st, 3,5,7 day, injected dose be 2OD/ only/time (200 microlitre tail vein injection), influenza virus is inoculated by collunarium mode, and dosage of inoculation is 2500pfu/
(3) monitor Mouse Weight Temperature changing situation every day, statistic fluid Influenza Virus is on Mouse Weight change and the impact (result is as Fig. 1 and 2) of Temperature changing and the impact (result is as Fig. 3) of fatality rate.
Although above the present invention is described in detail with a general description of the specific embodiments, on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.

Claims (8)

  1. The application of 1.miR-23a in the medicine of preparation treatment influenza.
  2. 2. application according to claim 1, is characterized in that, described application comprises the medicine preparing resisiting influenza virus.
  3. 3. application according to claim 2, is characterized in that, described influenza virus is influenza A virus.
  4. 4. the application according to claim 1 or 3, is characterized in that, comprises miR-23a and pharmaceutically acceptable carrier is composite makes pharmaceutical composition.
  5. 5. a pharmaceutical composition, is characterized in that, described pharmaceutical composition take miR-23a as active component.
  6. 6. pharmaceutical composition according to claim 5, is characterized in that, described pharmaceutical composition contains miR-23a and pharmaceutically acceptable carrier.
  7. 7. the pharmaceutical composition according to claim 5 or 6, is characterized in that, described compositions is also containing other active component treating and/or preventing influenza.
  8. 8. the pharmaceutical composition according to claim 5 or 6, is characterized in that, described medicine acceptable carrier is in vivo-jetPEI.
CN201510425041.XA 2015-07-17 2015-07-17 A kind of applications of microRNA in the medicine for preparing treatment influenza Expired - Fee Related CN104940955B (en)

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Cited By (1)

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CN111089654A (en) * 2020-02-17 2020-05-01 深圳市刷新智能电子有限公司 Epidemic situation macro monitoring method and system based on wearable body temperature sensor

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Publication number Priority date Publication date Assignee Title
CN108342388A (en) * 2017-12-29 2018-07-31 中国科学院微生物研究所 MicroRNA hsa-mir-127-3p and the like, and express the application of the microRNA carrier
CN108342388B (en) * 2017-12-29 2021-03-30 中国科学院微生物研究所 Micro RNA hsa-mir-127-3p and analogue thereof, and application of micro RNA expression vector

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