Modulators of APOL1 expression
The present embodiments provide methods, compounds, and compositions useful for inhibiting APOL1 expression, which may be useful for treating, preventing, or ameliorating a disease associated with APOL1.
1. A compound according to the following formula (SEQ ID NO: 1164):
or a pharmaceutically acceptable salt thereof.
2. A compound or a pharmaceutically acceptable salt thereof comprising a modified oligonucleotide, wherein the modified oligonucleotide is 16 linked nucleosides in length and has the nucleobase sequence consisting of the nucleobase sequence of SEQ ID NO: 1164, wherein the modified oligonucleotide has a gap segment consisting of nine linked deoxynucleosides;
a 5′ wing segment consisting of three linked nucleoside; and
a 3′ wing segment consisting of four linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment; wherein the 5′ wing segment consists of cEt nucleosides; wherein the 3′ wing segment consists of a cEt nucleoside, a cEt nucleoside, a cEt nucleoside, and 2′-O-methoxyethyl nucleoside in the 5′ to 3′ direction; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine.
3. The compound of claim 1 or claim 2 , wherein the pharmaceutically acceptable salt is a sodium salt.
4. The compound of claim 1 or claim 2 , wherein the pharmaceutically acceptable salt is a potassium salt.
5. A composition comprising the compound of claim 1 or claim 2 and a pharmaceutically acceptable carrier.
6. A method of inhibiting expression of APOL1 in a cell comprising contacting the cell with a compound according to claim 1 or claim 2 , thereby inhibiting expression of APOL1 in the cell.
7. The method of claim 6 , wherein the cell is in the kidney of an individual.