CTLA-4 aptamer conjugates
Provided herein are, inter alia, nucleic acid compounds useful for targeting CTLA-4-expressing cells and modulating cell activity of the CTLA-4-expressing cells. The compositions provided herein may be part of pharmaceutical compositions and may be used for treatment of cancer, inflammatory diseases, infectious diseases or metabolic diseases.
1. A nucleic acid compound comprising a monomeric CTLA-4 aptamer nucleic acid conjugated to a Signal Transducer and Activator of Transcription 3 (STAT3) antisense nucleic acid.
2. The nucleic acid compound of claim 1 , wherein the STAT3 antisense nucleic acid is STAT3 siRNA.
3. The nucleic acid compound of claim 1 , wherein the monomeric CTLA-4 aptamer nucleic acid is conjugated to the STAT3 antisense nucleic acid through a linker.
4. The nucleic acid compound of claim 3 , wherein the linker comprises a non-nucleic acid spacer.
5. The nucleic acid compound of claim 4 , wherein the non-nucleic acid spacer connects the STAT3 antisense nucleic acid to the 3′ terminal end of the linker nucleic acid sequence.
6. The nucleic acid compound of claim 3 , wherein the linker connects the STAT3 antisense nucleic acid to the 3′ terminal end of the monomeric CTLA-4 aptamer nucleic acid.
7. The nucleic acid compound of claim 1 , wherein the monomeric CTLA-4 aptamer nucleic acid is conjugated to the STAT3 antisense nucleic acid through a hybridized nucleic acid overhang.
8. The nucleic acid compound of claim 1 , wherein the monomeric CTLA-4 aptamer nucleic acid comprises SEQ ID NO:1.
9. A method of treating melanoma in a subject in need thereof, the method comprising administering to the subject an effective amount of the nucleic acid compound of claim 1 .
10. A method of treating renal cell carcinoma in a subject in need thereof, the method comprising administering to the subject an effective amount of the nucleic acid compound of claim 1 .
11. A method of treating lymphoma in a subject in need thereof, the method comprising administering to the subject an effective amount of the nucleic acid compound of claim 1 .
12. A method of treating colon cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the nucleic acid compound of claim 1 .
13. A method of treating melanoma in a subject in need thereof, the method comprising administering to the subject an effective amount of the nucleic acid compound of claim 2 .
14. A method of treating renal cell carcinoma in a subject in need thereof, the method comprising administering to the subject an effective amount of the nucleic acid compound of claim 2 .
15. A method of treating lymphoma in a subject in need thereof, the method comprising administering to the subject an effective amount of the nucleic acid compound of claim 2 .
16. A method of treating colon cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the nucleic acid compound of claim 2 .
17. A method of treating melanoma, renal cell carcinoma, lymphoma, or colon cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the nucleic acid compound of claim 8 .