CN104940955B - A kind of applications of microRNA in the medicine for preparing treatment influenza - Google Patents
A kind of applications of microRNA in the medicine for preparing treatment influenza Download PDFInfo
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- CN104940955B CN104940955B CN201510425041.XA CN201510425041A CN104940955B CN 104940955 B CN104940955 B CN 104940955B CN 201510425041 A CN201510425041 A CN 201510425041A CN 104940955 B CN104940955 B CN 104940955B
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Abstract
The present invention relates to applications of the miR 23a in the medicine for preparing treatment influenza.And a kind of pharmaceutical composition using miR 23a as active component, pharmaceutical composition provided by the present invention can suppress the pathogenic process of influenza virus by miR 23a.
Description
Technical field
The present invention relates to biological technical field, specifically, being related to a kind of microRNA in the medicine for preparing treatment influenza
Application.
Background technology
MicroRNA (tiny RNA) is one section of Microrna by 20-24 base composition, and it is in plant, animal, microorganism
And it is widely present in fractionated viral.The effects of microRNA in vivo after transcription mainly by way of adjusting to said target mrna
Translation process be adjusted.Shaping modes difference in different plant species, microRNA is main in plant and target
MRNA complete complementaries are translated to regulate and control mRNA, and microRNA only needs seed region sequence and target in animal body in contrast to this
Gene mRNA sequence complementary pairing is possible to regulate and control the gene.
Influenza A virus (Influenza A) is the RNA virus of a kind of serious threat human health, influenza A virus
For common influenza virus, it is easiest to morph, the hypotype of influenza A virus is then known as " bird flu ", bird flu
(Bird Flu) is a kind of acute infectious disease as caused by avian influenza virus, can infect the mankind after viral gene variation, infect
Symptom afterwards is mainly shown as high fever, cough, runny nose, myalgia etc., most a variety of with serious pneumonia, severe patient's heart, kidney etc.
Organ failure causes death, and case fatality rate is very high.This disease can pass through a variety of ways such as alimentary canal, respiratory tract, skin injury and eye conjunctiva
Footpath is propagated, and personnel and vehicle contact are to propagate an important factor for this is sick.
MiR-23a is located on No. 19 chromosome of human body, and a microRNA gene is formed with miR-24 and miR-27a
Cluster.The microRNA gene clusters possess single promoter sequence, can independently be transcribed.Grinding for miR-23a at present
Study carefully and have been reported that and think that it can suppress the development of bone-marrow-derived lymphocyte and maturation by suppressing transcription factor PU.1.Also evidence shows
MiR-23a can target SHP2 genes, promote the generation of red blood cell by reducing SHP2 expression.C-Myc as transcription because
Son can combine with the promoter region in miR-23a gene clusters reaches gene tune so as to suppress the transcription of the microRNA gene clusters
The function of section.Such as c-Myc suppression miR-23a expression causes the up-regulation of its target molecules glutaminase most in tumour cell
Cancer cell metabolism is influenceed eventually.In addition to c-Myc signal paths, the p65 albumen in NFkb signal paths can also be with miR-23a
Promoter region in gene cluster combines the expression for suppressing miR-23a.Also there are some researches show the CD8 positive T cells in activation in the recent period
Middle miR-23a expression is lowered, and the expression for suppressing miR-23a can improve killing ability of the T cell to tumour cell.In people's blood
MiR-23a can be resisted by TNF α by targetting Caspase7 and STK4 reductions Caspase3 level in endothelial cell
Caused apoptotic effect.But there is presently no the relevant report for suppressing influenza virus with miR-23a.
The content of the invention
It is an object of the invention to provide a kind of pharmaceutical composition containing miRNA for suppressing influenza virus, so as to be to control
Treat influenza virus and a kind of effective way is provided.
Influenza virus has the characteristics of mutation ability is strong, therefore specific targeting is not enough to answer infected by influenza to dash forward
Become.MicroRNA be one section of small fragment RNA its mainly expressed by way of non-fully matching come regulatory gene, therefore can have
Effect avoids the effect of missing the target triggered due to virus mutation.
The present inventor has found that miR-23a has anti-current during research suppresses the treatment method of influenza virus
Sense acts on.
Therefore, the application the invention provides miR-23a in the medicine for preparing treatment influenza.
Optionally, the application includes preparing the medicine of resisiting influenza virus.
Optionally, the influenza virus is influenza A virus.
Optionally, including by miR-23a and pharmaceutically acceptable carrier compounding pharmaceutical composition is made.
Optionally, described pharmaceutical composition is using mir-23a as active component.
Optionally, described pharmaceutical composition contains miR-23a and pharmaceutically acceptable carrier.
Optionally, other active components of the composition also containing treatment and/or flu-prevention.
Optionally, the carrier is in vivo-jetPEI.
Pharmaceutical composition provided by the present invention can suppress influenza virus to mitigate influenza virus by miR-23a
Fatal rate, the negative effect brought by virus mutation can be reduced.
Brief description of the drawings
Fig. 1 is the influence of miR-23a activator and antagonist to C57 mouse weights.
Fig. 2 is the influence of miR-23a activator and antagonist to C57 mouse temperatures.
Fig. 3 is the influence of miR-23a activator and antagonist to C57 mouse survival rates.
Embodiment
Below will the present invention is described in detail by embodiment.
In the present invention, term " miR-23a " refer to comprising miR-23a RNA sequence or its homologous sequence it is small
RNA.The miR-23a in various sources as is generally known in the art, for example, people, mouse, rabbit etc., these homologous sequences are all contained in the present invention
Term miR-23a in.Also it is substituted, lacks or adds comprising above-mentioned naturally occurring miR-23a sequences in the term of the present invention
Add one or several nucleotides, or still there is the derivative RNA of miR-23a bioactivity after biology chemical modification.This hair
In bright, the artificial synthesized and miR- with miR-23a biological activities that can be obtained by buying commercial goods mode
23a analogies fall within protection scope of the present invention.A kind of for example, miR-23a analogies miR- well known in the art
23aagomir sequence (lucky agate gene, catalog number (Cat.No.) as shown in SEQ ID No.1：B06001)：
AUCACAUUGCCAGGGAUUUCCAAAUCCCUGGCAAUGUGAUUU
In addition, miR-23a of the present invention can also be precursor forms, miR-23a precursors refer to be administered object
Precursor intracellular or that miR-23a can be formed in vivo.The method for obtaining naturally occurring miR-23a precursors is this
Well known to art personnel.
As well known to those skilled in the art, miR-23a encoding gene is located on No. 19 chromosome of human body, with miR-24 and
MiR-27a forms a microRNA gene cluster.Its initial transcription product forms the miR- of maturation after a series of processing
23a.MiR-23a precursors only just have corresponding biological function after the miR-23a of maturation is processed into.
Composition provided by the present invention can be used for preventing and/or treat influenza infection and by influenza virus
Related symptoms caused by infection and disease.MiR-23a of the invention containing effective dose in the composition.
In the present invention, the pharmaceutically acceptable carrier includes various excipient, diluent and adjuvant.Carrier itself
It is not necessary active component, and does not have undue toxicity after use.This kind of carrier includes but is not limited to：Physiological saline, delay
Fliud flushing, glucose, water, glycerine, ethanol etc..
In one embodiment of the invention, the carrier is the mixed of in vivo-jetPEI, miR-23a and the carrier
Conjunction proportion is 1 μ g：0.15-0.2 μ l, preferable ratio are 1 μ g:0.2μl.
In one embodiment of the invention, the form of the composition is suitable for：Direct naked RNA injections, lipid
Body parcel RNA direct injections, breeding unsoundness bacterium carry DNA method or replication defective adenoviral carries target DNA method etc..
The miR-23a of present invention effective dose can be entered with the pattern of administration and the order of severity etc. of disease to be treated
The corresponding adjustment of row.The selection of preferable effective dose can be integrated each factor by those of ordinary skill in the art to determine.It is described
Factor includes but is not limited to：MiR-23a pharmacokinetic parameter, the health status of treated patient, body weight, method of administration
Deng.
In one embodiment of the invention, the main formulation of the pharmaceutical composition is isotonic D/W, substantially
In disease development mid-term stage administration, it is administered once within every two days, administration every time is carried out according to miR-23a nucleic acid 38-42 μ g.
In the present invention, the method for administration of described pharmaceutical composition is intravenous, via arterial infusion or local injection etc., also may be used
To be administered using medicine-feeding technology well-known to those skilled in the art.
The pharmaceutical composition of the present invention can combine with other treatment means, the prevention and treatment for influenza virus.
Embodiment 1
(1) experiment material：C57 mouse used are purchased from Beijing Vital River Experimental Animals Technology Co., Ltd.；MiR-23a swashs
Dynamic agent (miR-23a agomir, catalog number (Cat.No.)：) and antagonist (miR-23a antagomir, catalog number (Cat.No.) B06001：B05001)
Purchased from lucky agate gene.
(2) totally 3 groups of experiments, every group of 10 mouse respectively at first 1 day of virus infected flow Influenza Virus A/WSN/33 (H1N1) with
And the 1st, 3,5,7 day injection agomir and antagomir after infection, injection dosage are 2OD//(200 microlitres of tail veins notes
Penetrate), influenza virus is inoculated with by collunarium mode, and dosage of inoculation is 2500pfu/
(3) mouse weight Temperature changing situation is monitored daily, and mouse weight is changed statistics influenza virus and Temperature changing
Influence (result such as Fig. 1 and 2) and fatal rate influence (result such as Fig. 3).
Although above the present invention is described in detail with a general description of the specific embodiments,
On the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Cause
This, these modifications or improvements, belong to the scope of protection of present invention without departing from theon the basis of the spirit of the present invention.
Claims (5)
- Applications of the 1.miR-23a in the medicine for preparing treatment influenza, the nucleotide sequence such as SEQ ID of the miR-23a Shown in NO.1.
- 2. application according to claim 1, it is characterised in that the application includes preparing the medicine of resisiting influenza virus.
- 3. application according to claim 2, it is characterised in that the influenza virus is influenza A virus.
- 4. the application according to claim 1 or 3, it is characterised in that including miR-23a and pharmaceutically acceptable carrier are answered It is configured to pharmaceutical composition.
- 5. a kind of be used to treat the pharmaceutical composition of influenza, it is characterised in that described pharmaceutical composition using miR-23a for it is active into Point, containing miR-23a and pharmaceutically acceptable carrier, other active components also containing treatment and/or flu-prevention, the medicine The acceptable carrier of thing is in vivo-jetPEI；The nucleotide sequence of the miR-23a is as shown in SEQ ID NO.1.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
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| 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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| CN101368213A (en) * | 2008-10-13 | 2009-02-18 | 南京大学 | Blood serum minuteness ribonucleic acid reagent kit and application in early diagnosis of hepatitis B |
| CN102218144B (en) * | 2010-04-13 | 2016-03-02 | 江苏命码生物科技有限公司 | A kind ofly regulate method of miRNA content in organism and uses thereof |
| CN102406653B (en) * | 2010-09-21 | 2015-05-06 | 中国人民解放军第二军医大学 | Anti-virus effect, implementation method and purpose of miRNA(ribose nucleic acid) |
| WO2013155980A1 (en) * | 2012-04-19 | 2013-10-24 | 中国科学院上海生命科学研究院 | Auto-immune disease-related microrna and use thereof |
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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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