Treatment of idiopathic pulmonary fibrosis using RNA complexes that target connective tissue growth factor
In certain aspects, provided herein are RNA complexes (e.g., asymmetric RNA complexes, such as asiRNAs or cell penetrating asiRNAs) that inhibit CTGF expression and are therefore useful for treating idiopathic pulmonary fibrosis.
1. An RNA complex comprising
an antisense strand that has the nucleotide sequence of SEQ ID NO: 262 that is 29 nt in length and having sequence complementarity to an CTGF mRNA sequence; and
a sense strand of 15 to 17 nt in length having sequence complementarity to the antisense strand,
wherein the antisense strand and the sense strand form a complex in which the 5′ end of the antisense strand and the 3′ end of the sense strand form a blunt end.
2. The RNA complex of claim 1 , wherein the sense strand is of 16 nt in length.
3. The RNA complex of claim 2 , wherein the sense strand has the nucleotide sequence of SEQ ID NO: 257.
4. The RNA complex of claim 1 or 2 , wherein the RNA complex comprises a chemical modification.
5. The RNA complex of claim 4 , wherein the chemical modification is a 2′-O-methylated nucleoside, a phosphorothioate bond or a hydrophobic moiety.
6. The RNA complex of claim 5 , wherein the RNA complex comprises a hydrophobic moiety.
7. The RNA complex of claim 6 , wherein the hydrophobic moiety is a cholesterol moiety.
8. The RNA complex of claim 4 , wherein the RNA complex is capable of penetrating the cellular membrane of a cell in the absence of a delivery vehicle.
9. A method of treating idiopathic pulmonary fibrosis in a subject comprising administering to the subject an RNA complex of claim 1 or 2 .
10. The method of claim 9 , comprising administering the RNA complex to the respiratory tract of the subject.
11. The method of claim 9 , wherein the RNA complex is administered intravenously, parenterally, or by inhalation.
12. A pharmaceutical composition comprising an RNA complex of claim 1 or 4 and a pharmaceutically acceptable carrier.