Composition for inhibiting CTGF expression
A composition according to an embodiment of the present invention includes nucleic acid molecules which are capable of effectively inhibiting the expression level of connective tissue growth factor (CTGF) and collagen by RNA interference (RNAi), thereby preventing or treating a variety of fibroproliferative diseases due to overexpression of CTGF or collagen.
1. A composition comprising: a nucleic acid molecule comprising at least one selected from the group consisting of:
(i) siRNA comprised of a sense RNA having the sequence of SEQ ID NO: 1 and an antisense RNA having the sequence of SEQ ID NO: 2; (ii) dsRNA comprised of a strand having a sequence of SEQ ID NO: 3 and another strand complementary thereto; (iii) dsRNA comprised of a strand having a sequence of SEQ ID NO: 57 and another strand complementary thereto; (iv) dsRNA comprised of a strand having a sequence of SEQ ID NO: 60 and another strand complementary thereto; and
a porous silica particle,
wherein the nucleic acid molecule is loaded on a surface or inside the pores of the porous silica particle; and
the porous silica particle is characterized in that an average pore diameter ranges from 5 to 100 nm, and t, at which an absorbance ratio in the following Equation 1 becomes 1/2, is 24 or more:
At/Ao [Equation 1]
wherein Ao is absorbance of the porous silica particle measured by putting 5 ml of suspension containing 1 mg/ml of porous silica particle into a cylindrical permeable membrane having pores with a pore diameter of 50 kDa:
15 ml of the same solvent as the suspension comes into contact with an outside of the permeable membrane, and the inside/outside of the permeable membrane are horizontally stirred at 60 rpm and at 37° C.;
pH of the suspension is 7.4; and
A t indicates absorbance of the porous silica particle measured after lapse of “t” hours since Ao was measured.
2. The composition of claim 1 , wherein the nucleic acid molecule comprises siRNA comprised of a sense RNA having the sequence of SEQ ID NO: 1 and an antisense RNA having the sequence of SEQ ID NO: 2; or dsRNA comprised of a strand having a sequence of SEQ ID NO: 3 and another strand complementary thereto.
3. The composition of claim 1 , wherein each of the sense RNA and the antisense RNA further comprises a sequence of UU or dTdT at 3′-terminals of the sense RNA and the antisense RNA sequence.
4. The composition of claim 1 , wherein the porous silica particle is positively charged or uncharged at neutral pH on an outer surface thereof or an inside of the pores.
5. The composition of claim 1 , wherein the porous silica particle has hydrophilic or hydrophobic functional groups.
6. The composition of claim 1 , wherein the nucleic acid molecule is siRNA comprised of a sense RNA having the sequence of SEQ ID NO: 1 and an antisense RNA having the sequence of SEQ ID NO: 2.
7. The composition of claim 1 , wherein the nucleic acid molecule is dsRNA comprised of a strand having a sequence of SEQ ID NO: 3 and another strand complementary thereto.
8. The composition of claim 1 , wherein the nucleic acid molecule is at least one selected from the group consisting of (i) dsRNA comprised of a strand having a sequence of SEQ ID NO: 57 and another strand complementary thereto, and (ii) dsRNA comprised of a strand having a sequence of SEQ ID NO: 60 and another strand complementary thereto.
9. A method for treating a fibroproliferative disease, the method comprising administering the composition of claim 1 to subject in need thereof.
10. The method of claim 9 , wherein the fibroproliferative disease is at least one selected from the group consisting of hypertrophic scar, keloid, pulmonary fibrosis, liver fibrosis, kidney fibrosis, cystic fibrosis, myelofibrosis, post-peritoneal fibrosis, scleroderma, systemic sclerosis, radiation-induced fibrosis, myocardial fibrosis, biliary fibrosis, renal sclerosis, subretinal fibrosis, diabetic retinopathy, Duken's muscular dystrophy, diabetic kidney disease, chronic renal failure, fatty hepatitis, proliferative vitreoretinopathy, musculoskeletal tumor, osteosarcoma, rhabdomyosarcoma, colorectal cancer, pancreatic cancer, sarcoidosis, macular degeneration, vitreoretinopathy, keratitis, pterygium, ophthalmology disease, uterine fibroids, glomerulonephritis, human immuno-deficient viral renal disease, acute respiratory distress syndrome, chronic obstructive pulmonary disease, rheumatoid arthritis, polymyositis and vascular stenosis.