Stabilized HNF4A saRNA compositions and methods of use
The invention relates to saRNA targeting an HNF4 a transcript and therapeutic compositions comprising said saRNA. Methods of using the therapeutic compositions are also provided.
1. A conjugate comprising a synthetic isolated small activating RNA (saRNA) and a carbohydrate moiety, wherein the saRNA up-regulates the expression of a target gene, wherein the target gene is HNF4a, wherein the saRNA is PR3-50-XD7663 (SEQ ID Nos. 133 and 134) or PR3-49-XD7667 (SEQ ID Nos. 139 and 140).
2. The conjugate of claim 1 , wherein the carbohydrate moiety is a N-Acetyl-Galactosamine (GalNAc) moiety.
3. The conjugate of claim 2 , wherein the GalNAc moiety is a triantennary GalNAc-cluster.
4. A synthetic isolated small activating RNA (saRNA) comprises at least one chemical modification, wherein the saRNA up-regulates the expression of a target gene, wherein the target gene is HNF4a, wherein the saRNA is PR3-50-XD7663 (SEQ ID Nos. 133 and 134) or PR3-49-XD7667 (SEQ ID Nos. 139 and 140).
5. A pharmaceutical composition comprising the conjugate of claim 1 and at least one pharmaceutically acceptable excipient.
6. A method of delivering an saRNA to cells comprising administering the conjugate of claim 1 to cells without any transfection agents.
7. A method of up-regulating the expression of a target gene, comprising administering the conjugate of claim 1 , wherein the target gene is HNF4a.
8. A pharmaceutical composition comprising the saRNA of claim 4 and at least one pharmaceutically acceptable excipient.
9. A method of up-regulating the expression of a target gene, comprising administering the saRNA of claim 4 , wherein the target gene is HNF4a.