IP Library › Granted Patent US 12,312,588
Granted Patent B2
US 12,312,588 · App. 18/205,390 · Granted May 27, 2025

Nucleolin-targeting aptamers and methods of using the same

Inventors: Bruce A. Sullenger (Durham, NC); Michael Goldstein (Durham, NC); Elizabeth D. Pratico (Durham, NC); Michael Kastan (Durham, NC); Bethany Gray (Durham, NC)
Assignee: Duke University
C12N15/115A61P35/00C12N2310/16
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Quick Facts
Patent No.
US 12,312,588
App. No.
18/205,390
Granted
May 27, 2025
Kind
B2
Abstract

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.

Claims (21)

1. An aptamer comprising

a polynucleotide having at least 80% sequence identity to any one of SEQ ID NOS: 1-12, 22-473, 475-479, 481, 483-484, 486, 490-502, or 504-515,

wherein the polynucleotide comprises an unmodified form or comprises 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: 22-473 or a portion thereof.

3. The aptamer of claim 1 , wherein the dissociation constant (K D ) of the aptamer for a nucleolin protein is less than 100 nanomolar (nM).

4. The aptamer of claim 1 , wherein the polynucleotide comprises an RNA polynucleotide.

5. 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.

6. The aptamer of claim 1 , wherein the polynucleotide comprises a 5′ linker and/or a 3′ linker.

7. The aptamer of claim 1 , wherein the polynucleotide further comprises an agent.

8. The aptamer of claim 7 , 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.

9. The aptamer of claim 8 , 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.

10. The aptamer of claim 7 , wherein the polynucleotide and the agent are linked by a covalent bond or a tag system.

11. A dimer, trimer, or tetramer comprising the aptamer of claim 1 .

12. A method for treating cancer in a subject comprising administering to the subject a therapeutically effective amount of the composition of claim 1 .

13. The method of claim 12 , further comprising administering a chemotherapeutic agent or radiation therapy to the subject.

14. The method of claim 13 , wherein the composition is administered prior to the administration of the chemotherapeutic agent or the radiation therapy.

15. The method of claim 12 , wherein the cancer is colon cancer.

16. The method of claim 12 , wherein the subject is a mammal.

17. A method of labeling or inhibiting nucleolin comprising contacting nucleolin with the composition of claim 1 .

18. The method of claim 17 , wherein the nucleolin is contacted by adding the composition to cells comprising nucleolin in vitro.

19. The method of claim 17 , wherein the nucleolin is contacted by administering the composition to a subject.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 6, 2023
From: SULLENGER, BRUCE A.; GOLDSTEIN, MICHAEL; PRATICO, ELIZABETH D.; KASTAN, MICHAEL; GRAY, BETHANY
To: DUKE UNIVERSITY
Reel/Frame 063865/0391 →
Continuity (3)
Division 16645762
Provisional Application 62555745 · Sep 8, 2017
Related Publication 20240150772A1 · May 9, 2024
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