Double-stranded oligo RNA targeted to amphiregulin and pharmaceutical composition comprising same for preventing or treating fibrosis or respiratory diseases

1. An siRNA comprising a sense strand comprising a sequence of SEQ ID NO: 59, 75, 80, 92, 98, 102, or 107, wherein when the sense strand comprises the sequence of SEQ ID NO: 107, the sense strand contains no more than 19 nucleotides; and an antisense strand having a sequence complementary thereto.

2. The siRNA of claim 1 , wherein SEQ ID NO: 107 is the sense strand.

3. The siRNA of claim 1 , wherein the siRNA comprises a sense strand comprising a sequence of SEQ ID NO: 59, 75, 80, 92, 98, or 102, and an antisense strand comprising a sequence complementary thereto.

4. The siRNA of claim 1 , wherein the sense strand or antisense strand of the siRNA comprise chemical modification wherein the chemical modification is any one or more selected from the group consisting of modification by substitution of a hydroxyl (—OH) group at the 2′ carbon position in a sugar structure in nucleotides with only one selected from the group consisting of methyl (—CH 3 ), methoxy (—OCH 3 ), amine (—NH 2 ), fluorine (—F), O-2-methoxyethyl, O-propyl, O-2-methylthioethyl, O-3-aminopropyl, O-3-dimethylaminopropyl, —O—N-methylacetamido and —O-dimethylamidooxyethyl groups;

modification by substitution of oxygen in a sugar structure in nucleotides with sulfur;

modification of a nucleotide bond into any one selected from the group consisting of a phosphorothioate bond, a boranophosphate bond, or a methyl phosphonate bond; and

modification into a peptide nucleic acid (PNA) type, a locked nucleic acid (LNA) type, or a unlocked nucleic acid (UNA) type.

5. The siRNA of claim 1 , wherein one or more phosphate groups are bound to a 5′-end of the antisense strand of the siRNA.

6. A double-stranded oligo RNA structure comprising a structure represented by the following Structural Formula 1:

A-X-R-Y-B  [Structural Formula 1]

wherein A is a hydrophilic material, B is a hydrophobic material, X and Y are each independently a simple covalent bond or linker-mediated covalent bond, and R is the siRNA of claim 1 .

7. The double-stranded oligo RNA structure of claim 6 , wherein the structure comprises a structure represented by the following Structural Formula 2:

wherein S and AS are a sense strand and an antisense strand of the siRNA of claim 6 , respectively, and A, B, X, and Y have the same definitions as those in claim 6 .

8. The double-stranded oligo RNA structure of claim 7 , wherein the structure comprises a structure represented by the following Structural Formula 3:

wherein A, B, X, Y, S, and AS have the same definitions as those in claims 6 , and 5′ and 3′ are a 5′-end and 3′-end of the sense strand of the siRNA, respectively.

9. The double-stranded oligo RNA structure of claim 6 ,

wherein the hydrophilic material is represented by the following Structural Formula 4:

(A′ m -J) n   [Structural Formula 4]

wherein A′ is a hydrophilic material monomer, J is a linker linking m hydrophilic material monomers to each other or linking m hydrophilic material monomers and the siRNA to each other, m is an integer of 1 to 15, n is an integer of 1 to 10,

wherein A′ is a compound selected from Compounds (1) to (3) represented as follows:

wherein G is selected for the group consisting of CH 2 , O, S and NH,

 and

wherein J is selected from the group consisting of PO 3 —, SO 3 , and CO 2 .

10. The double-stranded oligo RNA structure of claim 6 , wherein a molecular weight of the hydrophilic material is 200 to 10,000.

11. The double-stranded oligo RNA structure of claim 6 , wherein the hydrophilic material is polyethylene glycol (PEG), polyvinylpyrrolidone, or polyoxazoline.

12. The double-stranded oligo RNA structure of claim 6 , wherein a molecular weight of the hydrophobic material is 250 to 1,000.

13. The double-stranded oligo RNA structure of claim 6 , wherein the hydrophobic material is a steroid derivative, a glyceride derivative, glycerol ether, polypropylene glycol, an unsaturated or saturated (C12-C50) hydrocarbon, diacylphosphatidylcholine, fatty acid, phospholipid, lipopolyamine, lipid, tocopherol, or tocotrienol.

14. The double-stranded oligo RNA structure of claim 13 , wherein the steroid derivative is cholesterol, cholestanol, cholic acid, cholesteryl formate, chotestanyl formate, or cholestanyl amine.

15. The double-stranded oligo RNA structure of claim 13 , wherein the glyceride derivative is a mono-, di- or tri-glyceride.

16. The double-stranded oligo RNA structure of claim 6 , wherein each of the covalent bonds represented by X and Y is a non-degradable bond or degradable bond.

17. The double-stranded oligo RNA structure of claim 16 , wherein the non-degradable bond is an amide bond or phosphorylation bond.

18. The double-stranded oligo RNA structure of claim 16 , wherein the degradable bond is a disulfide bond, an acid degradable bond, an ester bond, an anhydride bond, a biodegradable bond or an enzymatically degradable bond.

19. A nanoparticle comprising the double-stranded oligo RNA structure of claim 6 .

20. The nanoparticle of claim 19 , wherein the nanoparticle comprises a mixture of double-stranded oligo RNA structures comprising siRNAs having different sequences from each other.

21. A pharmaceutical composition for preventing or treating fibrosis or respiratory diseases comprising the siRNA of claim 1 as an active ingredient.

22. A lyophilized formulation comprising the pharmaceutical composition of claim 21 .

23. A pharmaceutical composition for preventing or treating fibrosis or respiratory diseases comprising the double-stranded oligo RNA structure of claim 6 .

24. A lyophilized formulation comprising the pharmaceutical composition of claim 23 .

25. A pharmaceutical composition for preventing or treating fibrosis or respiratory diseases comprising the nanoparticle of claim 19 .

26. A lyophilized formulation comprising the pharmaceutical composition of claim 25 .

27. A method of preventing or treating fibrosis or respiratory diseases, comprising administering a pharmaceutical composition comprising the siRNA of claim 1 , a double-stranded oligo RNA structure comprising said siRNA, or a nanoparticle comprising said double-stranded oligo RNA structure.

28. The method of claim 27 , wherein the respiratory disease is COPD, asthma, acute or chronic bronchitis, allergic rhinitis, cough and phlegm, bronchitis, bronchiolitis, pharyngitis, tonsillitis, or laryngitis.

29. The method of claim 27 , wherein the fibrosis comprises IPF, cirrhosis, myelofibrosis, myocardial fibrosis, renal fibrosis, or pulmonary fibrosis.