Nucleolin-targeting aptamers and methods of using the same
Provided herein are compositions including aptamers capable of binding to and/or inhibiting the activity of nucleolin. Methods of treating cancer in a subject by administering such compositions are also provided.
1. An aptamer comprising
a polynucleotide having at least 80% sequence identity to any one of SEQ ID NOS: 480, 13-21, 485, 474, 482, 511, 487, 489, 503 or 488,
wherein the polynucleotide consists of an unmodified form or a modified form comprising at least one nucleotide base modification.
2. The aptamer of claim 1 , wherein the aptamer comprises a polynucleotide having at least 90% sequence identity to 5′-GGGAGAGAGGAAGAGGGAUGGG (SEQ ID NO: 491)-A Variable Region-CAUAACCCAGAGGUCGAUAGUACUGGAUCCCCCC (SEQ ID NO: 492)-3′, wherein the variable region comprises any one of SEQ ID NOS: 13-21 or a portion thereof.
3. The aptamer of claim 1 , wherein the aptamer comprises a polynucleotide having at least 90% sequence identity to SEQ ID NO: 480 (Ev3 Aptamer).
4. The aptamer of claim 1 , wherein the dissociation constant (K D ) of the aptamer for a nucleolin protein is less than 100 nanomolar (nM).
5. The aptamer of claim 1 , wherein the polynucleotide comprises an RNA polynucleotide.
6. The aptamer of claim 1 , wherein the polynucleotide comprises a modified form comprising at least one nucleotide base modification selected from the group consisting of a 2′fluoro modification, a 2′O-methyl modification, a 5′ modification, and a 3′modification.
7. The aptamer of claim 1 , wherein the polynucleotide comprises a 5′ linker and/or a 3′ linker.
8. The aptamer of claim 1 , wherein the polynucleotide further comprises an agent.
9. The aptamer of claim 8 , wherein the agent is a stability agent selected from the group consisting of polyethylene glycol (PEG), cholesterol, albumin, and Elastin-like polypeptide or a reporter moiety.
10. The aptamer of claim 9 , wherein said reporter moiety is selected from the group consisting of a fluorophore moiety, an optical moiety, a magnetic moiety, a radiolabel moiety, an X-ray moiety, an ultrasound imaging moiety, a photoacoustic imaging moiety, a nanoparticle-based moiety, and a. combination of two or more of the reporter moieties.
11. The aptamer of claim 8 , wherein the polynucleotide and the agent are linked by a covalent bond or a tag system.
12. A dimer, trimer, or tetramer comprising the aptamer of claim 1 .
13. A method for treating cancer in a subject comprising administering to the subject a therapeutically effective amount of the aptamer of claim 1 .
14. The method of claim 13 , further comprising administering a chemotherapeutic agent or radiation therapy to the subject.
15. The method of claim 14 , wherein the aptamer is administered prior to the administration of the chemotherapeutic agent or the radiation therapy.
16. The method of claim 13 , wherein the cancer is colon cancer.
17. The method of claim 13 , wherein the subject is a mammal.
18. A method of labeling or inhibiting nucleolin comprising contacting nucleolin with the aptamer of claim 1 .
19. The method of claim 18 , wherein the nucleolin is contacted by adding the aptamer to cells comprising nucleolin in vitro.
20. The method of claim 18 , wherein the nucleolin is contacted by administering the aptamer to a subject.