IP Library Granted Patent US 12,050,215
Granted Patent B2
US 12,050,215 · App. 15/776,346 · Granted Jul 30, 2024

Macromolecular structures and uses thereof

Inventors: Shuichi Takayama (Ann Arbor, MI); Cameron Louttit (Ann Arbor, MI); James J. Moon (Ann Arbor, MI); Taisuke Kojima (Ann Arbor, MI); Priyan Weerappuli (Ann Arbor, MI)
Assignee: The Regents of the University of Michigan
G01N33/544A01N25/10A01N57/16C12N11/089G01N2500/04
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Quick Facts
Patent No.
US 12,050,215
App. No.
15/776,346
Granted
Jul 30, 2024
Kind
B2
Abstract

Provided herein are macromolecular structures comprising charged macromolecules. In particular, provided herein are synthetic neutrophil extracellular traps and uses thereof.

Claims (26)

1. A system, comprising:

a plurality of in vitro generated three-dimensional structures comprising a network of a polyanion and a polycation, wherein said polyanion is a nucleic acid between approximately 1 kilobase and 1 megabase in length selected from the group consisting of genomic DNA, mitochondrial DNA, bacterial DNA, viral DNA, synthetic DNA, and combinations thereof, wherein said polycation is selected from the group consisting of a histone and a citrullinated histone wherein said structures comprise fibers of said polyanion and said polycation attached to the surface of a solid support; wherein said three-dimensional structures are made by a method, comprising:

dehydrating a first solution comprising a polyanion and an excipient; and

rehydrating said first solution with a second solution comprising a polycation such that said structures are formed.

2. The system of claim 1 , wherein said structures are spheres or discs with a diameter of 1 μm to 1 cm.

3. The system of claim 1 , wherein each of said fibers, or a bundle of said fibers, is approximately 7-500 nm in diameter and 0.1-100 μm in length.

4. The system of claim 1 , wherein said structures are in arrays.

5. The system of claim 1 , wherein said structures further comprise a test compound, diagnostic reagent, or therapeutic agent.

6. The system of claim 5 , wherein said test compound, diagnostic reagent, or therapeutic agent is selected from the group consisting of a charged compound, a nucleic acid, a cytokine, and a protein.

7. The system of claim 6 , wherein said test compound, diagnostic reagent, or therapeutic agent is selected from the group consisting of neutrophil elastase (HNE), LL-37, PAD-4, and Cathepsin-G.

8. The system of claim 1 , wherein said structures further comprise a cell or particle.

9. A method of killing or inhibiting the growth of a cell, comprising: contacting the cell with the three-dimensional structures of claim 1 .

10. The system of claim 1 , wherein said support is selected from the group consisting of a multi-well plate, a particle exterior, a well, a shell, a post, a hydrogel, an elastic surface, a curved surface, a cell, a tissue, a nucleic acid, and a microchannel.

11. The system of claim 1 , wherein said system further comprises a test compound, diagnostic biomolecule, or therapeutic agent.

12. The system of claim 11 , wherein said test compound, diagnostic biomolecule, or therapeutic agent is selected from the group consisting of a charged compound, a nucleic acid, a cytokine, and a protein.

13. A method, comprising:

a) contacting the composition of claim 1 with a test compound: and

b) measuring a change in at least one property of said structure in the presence of the test compound relative to absence of said test compound.

14. The method of claim 13 , wherein said test compound is a drug or disease related antibody.

15. The method of claim 13 , wherein said property is degradation of said structures or binding of disease biomolecule.

16. A method of screening a sample, comprising:

a) contacting the structures of the composition of claim 1 with a test sample comprising blood or a blood product; and

b) measuring binding of a biomolecule is said sample to said structures.

17. The system of claim 1 , wherein said polyanion is genomic DNA and said polycation is a histone.

18. The system of claim 1 , wherein said excipient is trehalose or dextran.

19. The method of claim 15 , wherein said binding of disease biomolecules are disease-related antibodies.

Assignments (2)
CONFIRMATORY LICENSE Recorded Sep 17, 2021
From: UNIVERSITY OF MICHIGAN
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 057515/0517 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2018
From: TAKAYAMA, SHUICHI; LOUTTIT, CAMERON; MOON, JAMES J.; KOJIMA, TAISUKE; WEERAPPULI, PRIYAN
To: THE REGENTS OF THE UNIVERSITY OF MICHIGAN
Reel/Frame 046543/0287 →
Continuity (2)
Provisional Application 62256321 · Nov 17, 2015
Related Publication 20200200741A1 · Jun 25, 2020