CTLA-4 aptamer siRNA species
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 cell activity modulating nucleic acid, wherein the nucleic acid is an anti-cancer siRNA.
2. The nucleic acid compound of claim 1 , wherein said anti-cancer siRNA is a FoxP3 siRNA.
3. The nucleic acid compound of claim 1 , wherein said anti-cancer siRNA is an anti-tyrosine kinase siRNA.
4. The nucleic acid compound of claim 1 , wherein said anti-cancer siRNA is a Signal Transducer and Activator of Transcription (STAT) siRNA.
5. The nucleic acid compound of claim 1 , wherein said monomeric CTLA-4 aptamer nucleic acid is conjugated to said cell activity modulating nucleic acid through a linker.
6. The nucleic acid compound of claim 5 , wherein said linker comprises a non-nucleic acid spacer.
7. The nucleic acid compound of claim 6 , wherein said non-nucleic acid spacer connects said cell activity modulating nucleic acid to the 3′ terminal end of said linker nucleic acid sequence.
8. The nucleic acid compound of claim 5 , wherein said linker connects said cell activity modulating nucleic acid to the 3′ terminal end of said monomeric CTLA-4 aptamer nucleic acid.
9. A mammalian cell, comprising a nucleic acid compound of claim 1 .
10. The mammalian cell of claim 9 , wherein said cell is a T cell.
11. The mammalian cell of claim 9 , wherein said cell comprises a vesicle comprising said nucleic acid compound.
12. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the nucleic acid compound of claim 1 .
13. A method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of a nucleic acid compound of claim 1 , thereby treating said subject.
14. A method of inhibiting growth of a CTLA-4-expressing cancer cell, said method comprising contacting a CTLA-4-expressing cancer cell with a nucleic acid compound of claim 1 , thereby inhibiting growth of said CTLA-4-expressing cancer cell.
15. The nucleic acid compound of claim 1 , wherein said monomeric CTLA-4 aptamer nucleic acid is connected to said cell activity modulating nucleic acid through a hybridized nucleic acid overhang.
16. The nucleic acid compound of claim 15 , wherein said monomeric CTLA-4 aptamer nucleic acid comprises a first single nucleic acid strand and said cell activity modulating nucleic acid comprises a second single nucleic acid strand, wherein said first nucleic acid strand includes a nucleic acid sequence that is complementary to a nucleic acid sequence of said second single nucleic acid strand thereby forming said hybridized nucleic acid overhang.