IP Library › Granted Patent US 12,433,910
Granted Patent B2
US 12,433,910 · App. 18/816,696 · Granted Oct 7, 2025

Polymer nanoparticle and DNA nanostructure compositions and methods for non-viral delivery

Inventors: Anthony D. Duong (Columbus, OH); Cherry Gupta (Columbus, OH); Kenneth R. Sims, Jr. (Columbus, OH); Danielle Huk (Columbus, OH); Jacob Lilly (Columbus, OH); Stephanie M. Kute (Columbus, OH); Mike Koeris (Columbus, OH)
Assignee: BATTELLE MEMORIAL INSTITUTE
A61K31/7088A61K47/60A61K47/6935C08F293/005C12N15/113B82Y5/00B82Y30/00B82Y35/00B82Y40/00C08F2438/03C12N2310/11C12N2310/531
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Quick Facts
Patent No.
US 12,433,910
App. No.
18/816,696
Granted
Oct 7, 2025
Kind
B2
Abstract

The invention relates to polymer nanoparticle and DNA nanostructure delivery compositions for non-viral delivery, and methods therefor. More particularly, the invention relates to polymer nanoparticle delivery compositions, such as reversible addition-fragmentation chain transfer (RAFT) polymer compositions, and DNA nanostructure delivery compositions, such as DNA origami compositions, for the delivery of more than one payload, or for the delivery of a nucleic acid construct payload of 3 kB or more, and methods therefor.

Claims (36)

1. A composition comprising a polymer nanoparticle and a payload, wherein the polymer nanoparticle comprises a RAFT block copolymer that comprises:

a first block prepared from one or more monomer units, and having a molecular weight (M n ) in the range of about 20 kDa to about 80 kDa and a degree of polymerization in the range of about 20 to about 400;

a second block prepared from one or more monomer units covalently attached to the first block, and having a molecular weight (M n ) in the range of about 5 kDa to about 80 kDa and a degree of polymerization in the range of about 10 to about 500; and

wherein the RAFT block copolymer has one or more of an overall molecular weight (M n ) in the range of about 25 kDa to about 160 kDa, and overall degree of polymerization in the range of about 30 to about 900, and

wherein the payload comprises a nucleic acid.

2. The composition of claim 1 , wherein the payload is chemically bonded to the polymer nanoparticle.

3. The composition of claim 1 , wherein the payload is complexed with the polymer nanoparticle.

4. The composition of claim 3 , wherein the payload is complexed with the polymer nanoparticle through electrostatic interactions.

5. The composition of claim 1 , wherein the polymer nanoparticle has a size in the range of about of about 10 to about 60 nm.

6. The composition of claim 1 , wherein the first block is prepared from one or more monomer units selected from the group consisting of 2-dimethylaminoethyl acrylate, 2-(diethylamino) ethyl methacrylate, 2-(diisopropylamino) ethyl methacrylate, butyl methacrylate, ethyl acrylic acid, propyl acrylic acid, (hydroxyethyl) methacrylate, and methyl methacrylate.

7. The composition of claim 6 , wherein the second block is prepared from one or more monomer units selected from the group consisting of 2-dimethylaminoethyl acrylate, 2-(diethylamino) ethyl methacrylate, 2-(diisopropylamino) ethyl methacrylate, butyl methacrylate, ethyl acrylic acid, propyl acrylic acid, (hydroxyethyl) methacrylate, and methyl methacrylate.

8. The composition of claim 6 , wherein the second block is a random copolymer prepared from two different monomer units independently selected from the group consisting of 2-dimethylaminoethyl acrylate, 2-(diethylamino) ethyl methacrylate, 2-(diisopropylamino) ethyl methacrylate, butyl methacrylate, ethyl acrylic acid, propyl acrylic acid, (hydroxyethyl) methacrylate, and methyl methacrylate.

9. The composition of claim 6 , wherein the second block is a random copolymer prepared from three different monomer units independently selected from the group consisting of 2-dimethylaminoethyl acrylate, 2-(diethylamino) ethyl methacrylate, 2-(diisopropylamino) ethyl methacrylate, butyl methacrylate, ethyl acrylic acid, propyl acrylic acid, (hydroxyethyl) methacrylate, and methyl methacrylate.

10. The composition of claim 1 , wherein the first block is prepared from one of 2-dimethylaminoethyl acrylate, 2-(diethylamino) ethyl methacrylate, 2-(diisopropylamino) ethyl methacrylate, butyl methacrylate, ethyl acrylic acid, propyl acrylic acid, (hydroxyethyl) methacrylate, or methyl methacrylate.

11. The composition of claim 10 , wherein the second block is prepared from one or more monomer units selected from the group consisting of 2-dimethylaminoethyl acrylate, 2-(diethylamino) ethyl methacrylate, 2-(diisopropylamino) ethyl methacrylate, butyl methacrylate, ethyl acrylic acid, propyl acrylic acid, (hydroxyethyl) methacrylate, and methyl methacrylate.

12. The composition of claim 10 , wherein the second block is a random copolymer prepared from two different monomer units independently selected from the group consisting of 2-dimethylaminoethyl acrylate, 2-(diethylamino) ethyl methacrylate, 2-(diisopropylamino) ethyl methacrylate, butyl methacrylate, ethyl acrylic acid, propyl acrylic acid, (hydroxyethyl) methacrylate, and methyl methacrylate.

13. The composition of claim 10 , wherein the second block is a random copolymer prepared from three different monomer units independently selected from the group consisting of 2-dimethylaminoethyl acrylate, 2-(diethylamino) ethyl methacrylate, 2-(diisopropylamino) ethyl methacrylate, butyl methacrylate, ethyl acrylic acid, propyl acrylic acid, (hydroxyethyl) methacrylate, and methyl methacrylate.

14. The composition of claim 1 , wherein the second block is prepared from one or more monomer units selected from the group consisting of 2-dimethylaminoethyl acrylate, 2-(diethylamino) ethyl methacrylate, 2-(diisopropylamino) ethyl methacrylate, butyl methacrylate, ethyl acrylic acid, propyl acrylic acid, (hydroxyethyl) methacrylate, and methyl methacrylate.

15. The composition of claim 1 , wherein the second block is a random copolymer prepared from two different monomer units independently selected from the group consisting of 2-dimethylaminoethyl acrylate, 2-(diethylamino) ethyl methacrylate, 2-(diisopropylamino) ethyl methacrylate, butyl methacrylate, ethyl acrylic acid, propyl acrylic acid, (hydroxyethyl) methacrylate, and methyl methacrylate.

16. The composition of claim 1 , wherein the second block is a random copolymer prepared from three different monomer units independently selected from the group consisting of 2-dimethylaminoethyl acrylate, 2-(diethylamino) ethyl methacrylate, 2-(diisopropylamino) ethyl methacrylate, butyl methacrylate, ethyl acrylic acid, propyl acrylic acid, (hydroxyethyl) methacrylate, and methyl methacrylate.

17. The composition of claim 1 , wherein the first block comprises a first capping unit of the formula

wherein * represents a point of covalent attachment to the first block.

18. The composition of claim 1 , wherein the second block comprises a second capping unit of the formula

wherein * represents a point of covalent attachment to the second block, and R is-SC 2 -C 12 alkyl or C 6 H 5 .

19. The composition of claim 1 , wherein the nucleic acid is a DNA or an RNA.

20. The composition of claim 19 , wherein the nucleic acid is complexed with the polymer nanoparticle through electrostatic interactions.

21. The composition of claim 19 , wherein the nucleic acid is a DNA.

22. The composition of claim 21 , wherein the DNA is complexed with the polymer nanoparticle through electrostatic interactions.

23. The composition of claim 19 , wherein the nucleic acid is an RNA.

24. The composition of claim 23 , wherein the RNA is complexed with the polymer nanoparticle through electrostatic interactions.

25. The composition of claim 19 , wherein the nucleic acid has a size of 3 kB-kB or more.

26. The composition of claim 19 , wherein the nucleic acid has size of 6.5 kB or more.

27. The composition of claim 19 , wherein the nucleic acid has a size of 8.5 kB or more.

28. The composition of claim 1 , wherein the payload comprises one or more of the components of the CRISPR RNP system.

29. The composition of claim 28 , wherein the one or more of the components of the CRISPR RNP system includes a CRISPR-associated enzyme, a short guide RNA (sgRNA), and a donor DNA strand.

30. The composition of claim 29 , wherein the CRISPR-associated enzyme is Cas9.

Continuity (4)
Continuation 18444146 · Feb 16, 2024
Continuation 17542055 · Dec 3, 2021
Provisional Application 63121202 · Dec 3, 2020
Related Publication 20240415865A1 · Dec 19, 2024
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