CN114042079A

CN114042079A - Application of RNA in treating dilated cardiomyopathy and myocardial fibrosis

Info

Publication number: CN114042079A
Application number: CN202111560705.5A
Authority: CN
Inventors: 戴宇翔; 龚惠; 葛均波; 邹妍; 黄晨兴; 卢静; 林金钟
Original assignee: Zhongshan Hospital Fudan University
Current assignee: Shanghai Lanque Biomedical Co ltd; Zhongshan Hospital Fudan University
Priority date: 2021-12-20
Filing date: 2021-12-20
Publication date: 2022-02-15
Anticipated expiration: 2041-12-20
Also published as: CN114042079B

Abstract

The invention relates to application of RNA in treating dilated cardiomyopathy, myocardial fibrosis and myocardial apoptosis, belonging to the technical field of biological medicines. The invention provides an application of RNA in preparing a medicament for treating dilated cardiomyopathy and an application in preparing a medicament for treating myocardial fibrosis and myocardial apoptosis, wherein the sequence of the RNA is SEQ ID No.1, and uracil U in an RNA chain is replaced by pseudo U. The invention provides an effective treatment means for myocardial fibrosis, myocardial apoptosis and dilated cardiomyopathy, and provides a new path for delaying the occurrence, development and treatment of related heart diseases.

Description

Application of RNA in treating dilated cardiomyopathy and myocardial fibrosis

Technical Field

The invention relates to application of RNA in treating dilated cardiomyopathy, myocardial fibrosis and myocardial apoptosis, belonging to the technical field of biological medicines.

Background

Dilated Cardiomyopathy (DCM), a common cause of heart failure, is a severe heterogeneous pathological condition of the heart, characterized by ventricular dilatation, with systolic and diastolic dysfunction. Myocardial fibrosis is the pathological entity of extracellular matrix remodeling, often leading to increased myocardial stiffness, with both reactive (interstitial and perivascular) and reparative (surrogate) fibrosis in DCM, suggesting that inflammation and microvascular injury are involved in the disease process. In DCM patients, cardiac fibrosis is associated with poor prognosis and impaired response to therapeutic intervention. Suggesting that anti-fibrotic treatment may help improve cardiac function in the diseased heart. Fibroblasts are considered to be the primary cellular mediators of cardiac fibrosis and play an important role in regulating normal cardiac function and poor myocardial remodeling.

Expression of therapeutic proteins in vivo via mRNA has several advantages over delivery or modification of DNA: 1. messenger RNA is easier to deliver because it only needs to enter the cytoplasm rather than the nucleus to function. 2. Complications arising from transcriptional regulatory mechanisms are avoided and it does not permanently alter the genome, thus avoiding permanent and potentially fatal changes. 3. To overcome the nucleotide nature of natural RNA, which is inherently unstable and transient, the use of RNA as part of a therapeutically relevant organism was explored to increase transformation capacity by providing serum stability, increasing an inactive immune response. Modified mRNA (mod-mRNA) is a synthetic messenger rna (mRNA) in which some of the nucleosides are replaced with other naturally modified nucleosides or synthetic nucleoside analogs. In some cells, modRNA is used to induce production of the desired protein. It is widely studied as an alternative to natural mRNA therapy for the treatment of various diseases. The mRNA is a specific RNA sequence obtained by taking a linearized plasmid as a template, catalyzing by RNA polymerase and carrying out in vitro transcription by a one-step capping method in vitro. In a transcription system, cap1 cap analogues and Nucleoside Triphosphates (NTPs) are used as substrates; in the transcription process, pseudouracil (psi), 5-methylcytosine (5mC) or other artificial synthetic bases are used for replacing natural uridine triphosphate, cytidine triphosphate and the like to obtain modified mRNA, and partial or complete replacement of one or more types of bases is used, so that the half-life of corresponding therapeutic mRNA is greatly prolonged, and the expression level of a functional protein product in vitro and in vivo is higher.

Numerous studies have shown that the use of mod-RNA as a genetic information carrier can be effective in the treatment of both genetic and regenerative diseases. In order to fully exploit the therapeutic potential of mod-mRNA, it is highly desirable to develop new strategies to safely and efficiently modify targeting moieties of in vitro transcribed RNA (e.g., folate, antibody conjugates, and other desirable bioconjugates).

Disclosure of Invention

The invention aims to solve the technical problem of application of RNA in treating dilated cardiomyopathy and myocardial fibrosis.

In order to solve the above problems, the technical scheme adopted by the present invention is to provide an application of RNA in the preparation of a drug for treating dilated cardiomyopathy, wherein the sequence of the RNA is SEQ ID No.1, uracil U in the RNA strand is replaced by pseudouracil (Ψ), pseudouracil U; the RNA was designated DSC 2-mod-RNA;

the sequence of SEQ ID No.1 is:

GGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGAGCCACCAUGGCUGCAGUAGGUUCAAUGAGGUCUGGUUCACCAGCCUUUGGACUAGGGCAUCUAUUAACUCUGGCCAUUUUGGCCCUCGCUUCUGAUGCUUGUAAAGAGGUUGUCCUGCAGGUACCAAGUGAGCUCCCCGCCGAAAAGUUUGUCGGAAGAGUCAAUCUGAUGGAUUGUCUGAAGUCCGCCGACAUCGUGCAUUUGUCAGAUCCCGAUUUUCAGGUGCUAGAGGACGGGUCUGUCUACACCACCAGUUCCGUUGUGUUGUCCAGUGGCCAAAGGAGCUUCACAAUCUGGCUGUUCUCUACAGACAGCCAGGAGGAACGUGAGAUUAGCGUCCACCUGGAGGGGCCCGUAGAAGUACUAAACAAACGCCCUCAUACUGAGAAAGUCCUCAGCAGGGCUAAGCGGCGCUGGGCUCCCAUCCCGUGCUCCAUGCUGGAGAACAGUCUGGGUCCCUUCCCUCUGUUUCUCCAGCAGAUCCAGUCAGAUACGGCACAAAAUUAUACUAUCUACUACUCGAUCCGUGGACCUGGAGUGGACAAGGAACCUCUUAACCUAUUCUAUGUUGAAAGGGACACAGGCAAUCUGUACUGCACAGGGCGGGUGGAUCGCGAACAGUAUGAGUCAUUUGAGCUAACAGCUUUUGCCACCACCCCGGACGGAUACACCCCUGAAUAUCCACUGCCCCUUUUGAUUAAGAUCGAGGACGAGAAUGACAAUUACCCUAUAUUUACCCAGAAGCUCUACUCAUUCACUGUGCAAGAGAAUUCCCGGAUCGGCAGCAUUGUCGGAGAAGUGUGUGCUACCGAUCUGGAUGAGCCUGACACAAUGCACACUCGGCUUCGUUAUUCCAUCUUAGAGCAGAGCCCAUCACCACCUAUGUUGUUCACGAUGCAUCCUAGCACGGGUGUUAUCACCACCACCUCAGCUCAGCUCGACCGAGAACUCAUAGACAAGUACCAGCUGCUGAUUAAAGUCCAGGACAUGGACGGCCAGUACUUCGGACUGCACACCACAGCCAAGUGCAUCAUUACCAUUGAGGAUGUGAAUGACAACCUCCCUACGUUCACAAGGACUACUUACGUGACCUCCGUUGAAGAAAACACAGUAAAUGUCGAGAUCCUGAGGCUAACCGUGCAGGACAAAGACCUCGUCAAUAGCCCUAAUUGGCGAGCAAACUACACCAUCCUCAAAGGAAAUGAAAAUGGGAACUUUAAGAUUGUGACUGACCCGAAAACCAACGAGGGAAUACUGUGUGUGAUAAAACCCCUUGACUAUGAGGAGCGCCAACAAGUGACCCUCCAGAUUGGGGUUGUCAAUGAGGCACCGUACACAAGAGAAGCAAGCUCUAAAUCGCCCAUGAGUACAGCCACAGUGACUGUCACAGUUACUAACCAGGAUGAAGGACCUGAGUGUAUACCUCCCAUGCAGACUGUGAGAAUCCAAGAGAAUGUGCCAGUGGGUACACGGAACGAUGGCUACAAGGCCUAUGAUCCAGAGACUAGAAGUUCUUCUGGCAUUCGGUACAGGAAGCUUUCUGAUCCCAGGGGCUGGGUGACAGUGAACGAAGACUCUGGAUCCAUCACCAUCUUCCGUGCCCUCGAUCGAGAGGCAGAAACAGUUAGGAAUGGGAUCUAUAACAUUACAGUCUUAGCGUUAGAUGCCGACGGCAGAUCAUGCACCGGAACACUGGGAAUUAUCCUGGAAGACGUUAACGACAACGGGCCAUUUAUUCCAAAGCAGACAGUAGUCAUCUGCAAAGCGACGAUGAGCAGCGCAGAGAUUGUAGCUGUGGAUCUGGAUGAUCCAGUGAACGGGCCACCGUUUGACUUUUCACUGGAAUCCUCUGAUAGUGAGGUGCAGAGGAUGUGGAGGCUGACUAGAAUCAAUGACACCGCGGCCCGCUUGUCCUAUCAGAACGACCCUUCGUUUGGCAGCUAUGCCGUGCCAAUCCGAGUAACAGAUCGCCUCGGUCUCUCCAGUGUGACUACGCUGAAUGUGCUGGUCUGUGACUGUAUAACUGAAAGCGAUUGUACACUGCGGAGUGGAGAAAGAACAGGCUAUGCAGAUGUGAGGCUGGGCCCCUGGGCCAUAUUGGCGAUACUGUUAGGGAUUGCUCUGCUUUUCUGCAUCCUCUUUACUCUAGUUUGUUCUGUCUCCAGAGCAUCUAAGCAACAGAAAAUCCUUCCAGAUGACUUGGCACAGCAGAAUCUUAUCGUGAGUAACACUGAGGCCCCUGGAGACGAUAAGGUGUAUUCCACGAACGGCCUGACGACUCAGACCAUGGGGGCCAGCGGUCAAACCGCUUUCACUACCAUGGGGACCGGCGUGAAGUCAGGGGGACAGGAGACGAUUGAGAUGGUGAAAGGGGGUCAGCAAACGCUUGACAGUCGGCGCGGUGCAGGGUACCACCACCACACUUUAGAUCCAUGCCGAGGGGGCCACGUGGAGGUAGAUAACUACCGGCAUACCUACUCCGAAUGGUACAACUUCAUUCAGCCCCGUCUCGGAGACAAAGUUCAGUUCUGCCAUACUGACGACAACCAAAAGCUGGCUCAGGACUACGUCCUGACAUAUAACUAUGAAGGCAAGGGCAGUGCCGCUGGCUCCGUGGGCUGCUGCAGCGAUCUGCAGGAAGAGGAUGGCUUGGAAUUCCUGGACCACCUCGAACCCAAAUUCAGAACAUUGGCUGAGGUUUGUGCGAAGAGAUACCCGUACGACGUGCCGGACUACGCCUAAUAGGCGGCCGCUUAAUUAAGCUGCCUUCUGCGGGGCUUGCCUUCUGGCCAUGCCCUUCUUCUCUCCCUUGCACCUGUACCUCUUGGUCUUUGAAUAAAGCCUGAGUAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA。

the invention provides an application of RNA in preparing a medicament for treating myocardial fibrosis, wherein the sequence of the RNA is SEQ ID No.1, and uracil U in an RNA chain is replaced by pseudo U.

The invention provides an application of RNA in preparing a medicament for treating myocardial apoptosis, wherein the sequence of the RNA is SEQ ID No.1, and uracil U in an RNA chain is replaced by pseudo U.

The invention provides application of RNA in a non-diagnostic method and a non-therapeutic method, wherein the sequence of the RNA is SEQ ID No.1, and uracil U in an RNA chain is replaced by pseudo U.

The invention provides an application of RNA in preparing a medicament for treating dilated cardiomyopathy.

The invention provides application of RNA in preparing a medicament for treating myocardial fibrosis.

The invention provides an application of RNA in preparing a medicament for treating myocardial apoptosis.

Compared with the prior art, the invention has the following beneficial effects:

1) the DSC2-mod-RNA can effectively inhibit the fibrosis of the cardiac muscle and relieve the occurrence and development processes of dilated cardiac muscle. From this, it is considered that DSC2-mod-RNA can be used for clinical treatment of a disease associated with myocardial contractile function.

2) Patients with clinical DSC2 loss exhibit typical dilated cardiomyopathy dominated by right ventricular dilation. The invention constructs an dilated cardiomyopathy mouse model which mainly takes right ventricular dilatation caused by DSC2 deletion by simulating the phenotype of clinical patients. By cardiac ultrasounds monitoring the mice at different time points, the mice were injected with DSC2-modRNA at the interventricular site under cardiac ultrasounds after the right ventricle of the mice began to dilate. The experimental result shows that compared with a control group of mice with right ventricular dilated cardiomyopathy, the point injection DSC2-mod-RNA effectively inhibits the development of myocardial fibers, controls the deterioration of dilated cardiomyopathy and has a treatment effect on the dilated cardiomyopathy.

3) At present, the clinical application mainly aims to find the causes of diseases (such as infection control, autoimmune disease treatment or heart failure treatment and arrhythmia treatment), slow ventricular remodeling by selecting beta-blocker or ACEI drug treatment, or increase the blood ejection volume of the heart by applying cardiotonic and diuretic drugs to improve symptoms. Compared with the broad-spectrum treatment means of cardiomyopathy, the invention has certain treatment and disease progression slowing effects on cardiomyopathy through the modRNA DSC2 target treatment, and provides a new treatment means for the treatment prospect of dilated cardiomyopathy.

Drawings

FIG. 1 is a graph of heart and heart fibrosis following DSC2-mod-RNA treatment in a mouse model of right ventricular dominated dilated cardiomyopathy resulting from a deletion of DSC 2;

wherein panel A is a control group showing a marked enlargement of the heart; panel B is a DSC2-mod-RNA treated group showing smaller hearts and less pronounced cardiac fibrosis compared to the control group.

FIG. 2 is a graph of the change in cardiac fibrosis following DSC2-mod-RNA treatment in a mouse model of right ventricular dominated dilated cardiomyopathy resulting from a deletion of DSC 2;

wherein, the A picture is a healthy control group, the B picture is a dilated cardiomyopathy model control group, and the C picture is a dilated cardiomyopathy model DSC2-mod-RNA treatment group.

FIG. 3 is a graph of the change in apoptosis in a mouse model of right ventricular dominated dilated cardiomyopathy resulting from a deletion of DSC2 following treatment with DSC 2-mod-RNA;

FIG. 4 is a graph of DSC2-mod-RNA lipid nanoparticles expression after transfection of HEK 293A cells;

Detailed Description

In order to make the invention more comprehensible, preferred embodiments are described in detail below with reference to the accompanying drawings:

the invention provides an application of RNA in preparing a medicament for treating dilated cardiomyopathy, wherein the sequence of the RNA is SEQ ID No.1, and uracil U in an RNA chain is replaced by pseudo U.

Examples

mRNA preparation:

the mRNA is obtained by taking a PCR product containing a target sequence as a template and performing in vitro transcription by a one-step capping method. A Cap1 Cap analogue (m7G (5') ppp (5') (2' OMeA) pG (product EZ Cap # B8176 from APExBIO, Cap1), ATP, GTP, CTP, Pseudo-UTP (Pseudo-U, ApexBio, # B7972) was used in the transcription system to generate Pseudo-ouridine (Ψ) -modified mRNA of the Cap1 structure, which was purified by two-step chromatography to obtain high-purity mRNA.

2. Lipid nanoparticle preparation:

mRNA is ionizable (cationic) at low pH, two helper lipids (DSPC and cholesterol) and a pegylated lipid (DMPE-PEG2000) are coated into nanoparticles. The mRNA was purified by mixing mRNA dissolved in ultrapure water with 100. mu.mM citrate buffer 1 at pH 3.0: 1(v/v) to prepare an aqueous mRNA solution. The four lipid components (cationic lipid: cholesterol: DSPC: DMPE-PEG2000) were adjusted in ratio (50:10:38.5:1.5) and dissolved in ethanol (99.5%) to form a lipid solution. mRNA and lipid solutions were mixed in a nanoassmblr (precision nanosystems) microfluidic mixing system at an Aq: EtOH ═ 3: a volumetric mixing ratio of 1 and a constant total flow rate of 12mL/min, resulting in liposomal nanoparticles containing mRNA (LNP). The lipid nanoparticles are dialyzed, concentrated, filtered and stored.

3. Lipid nanoparticle transfected cells

The obtained lipid nanoparticles are respectively transfected into HEK 293A cells, and protein expression is detected by Western Blot after liquid culture. The results are shown in FIG. 3. The results showed that dsc2 mRNA was expressed in HEK 293A cells.

4. Animal experiment results:

FIG. 1 is a graph of heart and heart fibrosis following DSC2-mod-RNA treatment in a mouse model of right ventricular dominated dilated cardiomyopathy resulting from a loss of DSC 2; wherein panel A is a control group showing a marked enlargement of the heart; panel B is a DSC2-mod-RNA treated group showing smaller hearts and less pronounced cardiac fibrosis compared to the control group.

The heart size of the mouse is detected through the heart super, and when the heart cavity of the mouse becomes large, the drug intervention is carried out on the mouse. It was found through several experiments that the mice with dilated cardiomyopathy showed a marked enlargement of the heart after intraperitoneal injection with placebo in the control group, whereas the mice with DSC2-mod-RNA showed a smaller heart and less marked fibrosis in the heart than in the control group.

FIG. 2 is a graph of the change in cardiac fibrosis following DSC2-mod-RNA treatment in a mouse model of right ventricular dominated dilated cardiomyopathy resulting from a deletion of DSC 2; wherein, the A picture is a healthy control group, the B picture is a dilated cardiomyopathy model control group, and the C picture is a dilated cardiomyopathy model DSC2-mod-RNA treatment group.

The heart size of the mouse is detected through the heart super, and when the heart cavity of the mouse becomes large, the drug intervention is carried out on the mouse. Through multiple experiments, the mice with the heart disease show obvious fibrosis of the heart after the control group is injected with placebo in the abdominal cavity, but the symptoms of the fibrosis are inhibited after the mice with the heart disease are injected with DSC2-mod-RNA through cardiac super-guide lower ventricular interval points.

FIG. 3 is a graph of the change in apoptosis following DSC2-mod-RNA treatment in a mouse model of right ventricular dominated dilated cardiomyopathy resulting from a deletion of DSC 2; wherein, the A picture is a healthy control group, the B picture is a dilated cardiomyopathy model control group, and the C picture is a dilated cardiomyopathy model DSC2-mod-RNA treatment group.

The heart size of the mouse is detected through the heart super, and when the heart cavity of the mouse becomes large, the drug intervention is carried out on the mouse. Through multiple experiments, the heartburn mice show obvious heart apoptosis after the control group is subjected to intraperitoneal injection by using placebo, but the apoptosis is inhibited after the heartburn mice are subjected to ventricular-super-guided ventricular interval point injection by DSC 2-mod-RNA.

While the invention has been described with respect to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention. Those skilled in the art can make various changes, modifications and equivalent arrangements, which are equivalent to the embodiments of the present invention, without departing from the spirit and scope of the present invention, and which may be made by utilizing the techniques disclosed above; meanwhile, any changes, modifications and variations of the above-described embodiments, which are equivalent to those of the technical spirit of the present invention, are within the scope of the technical solution of the present invention.

Sequence listing

Application of <120> RNA in treating dilated cardiomyopathy and myocardial fibrosis

<160> 1

<170> SIPOSequenceListing 1.0

<210> 1

<211> 2994

<212> RNA

<213> Artificial Sequence (Artificial Sequence)

<400> 1

ggaaauaaga gagaaaagaa gaguaagaag aaauauaaga gccaccaugg cugcaguagg 60

uucaaugagg ucugguucac cagccuuugg acuagggcau cuauuaacuc uggccauuuu 120

ggcccucgcu ucugaugcuu guaaagaggu uguccugcag guaccaagug agcuccccgc 180

cgaaaaguuu gucggaagag ucaaucugau ggauugucug aaguccgccg acaucgugca 240

uuugucagau cccgauuuuc aggugcuaga ggacgggucu gucuacacca ccaguuccgu 300

uguguugucc aguggccaaa ggagcuucac aaucuggcug uucucuacag acagccagga 360

ggaacgugag auuagcgucc accuggaggg gcccguagaa guacuaaaca aacgcccuca 420

uacugagaaa guccucagca gggcuaagcg gcgcugggcu cccaucccgu gcuccaugcu 480

ggagaacagu cugggucccu ucccucuguu ucuccagcag auccagucag auacggcaca 540

aaauuauacu aucuacuacu cgauccgugg accuggagug gacaaggaac cucuuaaccu 600

auucuauguu gaaagggaca caggcaaucu guacugcaca gggcgggugg aucgcgaaca 660

guaugaguca uuugagcuaa cagcuuuugc caccaccccg gacggauaca ccccugaaua 720

uccacugccc cuuuugauua agaucgagga cgagaaugac aauuacccua uauuuaccca 780

gaagcucuac ucauucacug ugcaagagaa uucccggauc ggcagcauug ucggagaagu 840

gugugcuacc gaucuggaug agccugacac aaugcacacu cggcuucguu auuccaucuu 900

agagcagagc ccaucaccac cuauguuguu cacgaugcau ccuagcacgg guguuaucac 960

caccaccuca gcucagcucg accgagaacu cauagacaag uaccagcugc ugauuaaagu 1020

ccaggacaug gacggccagu acuucggacu gcacaccaca gccaagugca ucauuaccau 1080

ugaggaugug aaugacaacc ucccuacguu cacaaggacu acuuacguga ccuccguuga 1140

agaaaacaca guaaaugucg agauccugag gcuaaccgug caggacaaag accucgucaa 1200

uagcccuaau uggcgagcaa acuacaccau ccucaaagga aaugaaaaug ggaacuuuaa 1260

gauugugacu gacccgaaaa ccaacgaggg aauacugugu gugauaaaac cccuugacua 1320

ugaggagcgc caacaaguga cccuccagau ugggguuguc aaugaggcac cguacacaag 1380

agaagcaagc ucuaaaucgc ccaugaguac agccacagug acugucacag uuacuaacca 1440

ggaugaagga ccugagugua uaccucccau gcagacugug agaauccaag agaaugugcc 1500

aguggguaca cggaacgaug gcuacaaggc cuaugaucca gagacuagaa guucuucugg 1560

cauucgguac aggaagcuuu cugaucccag gggcugggug acagugaacg aagacucugg 1620

auccaucacc aucuuccgug cccucgaucg agaggcagaa acaguuagga augggaucua 1680

uaacauuaca gucuuagcgu uagaugccga cggcagauca ugcaccggaa cacugggaau 1740

uauccuggaa gacguuaacg acaacgggcc auuuauucca aagcagacag uagucaucug 1800

caaagcgacg augagcagcg cagagauugu agcuguggau cuggaugauc cagugaacgg 1860

gccaccguuu gacuuuucac uggaauccuc ugauagugag gugcagagga uguggaggcu 1920

gacuagaauc aaugacaccg cggcccgcuu guccuaucag aacgacccuu cguuuggcag 1980

cuaugccgug ccaauccgag uaacagaucg ccucggucuc uccaguguga cuacgcugaa 2040

ugugcugguc ugugacugua uaacugaaag cgauuguaca cugcggagug gagaaagaac 2100

aggcuaugca gaugugaggc ugggccccug ggccauauug gcgauacugu uagggauugc 2160

ucugcuuuuc ugcauccucu uuacucuagu uuguucuguc uccagagcau cuaagcaaca 2220

gaaaauccuu ccagaugacu uggcacagca gaaucuuauc gugaguaaca cugaggcccc 2280

uggagacgau aagguguauu ccacgaacgg ccugacgacu cagaccaugg gggccagcgg 2340

ucaaaccgcu uucacuacca uggggaccgg cgugaaguca gggggacagg agacgauuga 2400

gauggugaaa gggggucagc aaacgcuuga cagucggcgc ggugcagggu accaccacca 2460

cacuuuagau ccaugccgag ggggccacgu ggagguagau aacuaccggc auaccuacuc 2520

cgaaugguac aacuucauuc agccccgucu cggagacaaa guucaguucu gccauacuga 2580

cgacaaccaa aagcuggcuc aggacuacgu ccugacauau aacuaugaag gcaagggcag 2640

ugccgcuggc uccgugggcu gcugcagcga ucugcaggaa gaggauggcu uggaauuccu 2700

ggaccaccuc gaacccaaau ucagaacauu ggcugagguu ugugcgaaga gauacccgua 2760

cgacgugccg gacuacgccu aauaggcggc cgcuuaauua agcugccuuc ugcggggcuu 2820

gccuucuggc caugcccuuc uucucucccu ugcaccugua ccucuugguc uuugaauaaa 2880

gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2940

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 2994

Claims

1. The application of the RNA in the preparation of the medicine for treating dilated cardiomyopathy is characterized in that the sequence of the RNA is SEQ ID No.1, and uracil U in an RNA chain is replaced by pseudo U.

2. The application of RNA in preparing a medicament for treating myocardial fibrosis is characterized in that the sequence of the RNA is SEQ ID No.1, and uracil U in an RNA chain is replaced by pseudo U.

3. The application of RNA in preparing a medicine for treating myocardial apoptosis is characterized in that the sequence of the RNA is SEQ ID No.1, and uracil U in an RNA chain is replaced by pseudo U.

4. Use of an RNA having the sequence SEQ ID No.1 in a non-diagnostic method and a non-therapeutic method wherein uracil U is replaced with pseudo U in the RNA strand.

5. An application of RNA in preparing the medicines for treating dilated cardiomyopathy is disclosed.

6. An application of RNA in preparing the medicines for treating myocardial fibrosis.

7. An application of RNA in preparing the medicine for treating myocardial apoptosis is disclosed.