IP Library › Granted Patent US 12,691,166
Granted Patent B2
US 12,691,166 · App. 17/684,269 · Granted Jul 28, 2026

Antiviral vaccines using spherical nucleic acids

Inventors: Chad A. Mirkin (Wilmette, IL); Michelle Hope Teplensky (Evanston, IL); Max Everett Distler (Evanston, IL); Caroline Danielle Kusmierz (San Antonio, TX); Cassandra Elizabeth Callmann (Evanston, IL)
Assignee: NORTHWESTERN UNIVERSITY
A61K39/001192A61K39/39A61P35/00C12N15/1138A61K2039/55555A61K2039/55561
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Quick Facts
Patent No.
US 12,691,166
App. No.
17/684,269
Granted
Jul 28, 2026
Kind
B2
Abstract

Spherical Nucleic Acids (SNAs) are chemically well-defined nanoscale architectures comprised of nucleic acids densely arranged around a spherical nanoparticle core in a highly oriented fashion. SNAs are highly modular structures produced by chemical synthesis and programmed assembly, allowing for their rapid modification to incorporate novel viral antigens. The present disclosure provides a SNA comprising (a) a nanoparticle core; (b) a shell of oligonucleotides attached to the external surface of the nanoparticle core, the shell of oligonucleotides comprising one or more immunostimulatory oligonucleotides; and (c) a viral antigen encapsulated in the nanoparticle core.

Claims (44)

1 . A spherical nucleic acid (SNA) comprising:

(a) a nanoparticle core, wherein the nanoparticle core is a liposomal core or a lipid nanoparticle core;

(b) a shell of oligonucleotides attached to the external surface of the nanoparticle core, the shell of oligonucleotides comprising one or more immunostimulatory oligonucleotides; and

(c) a coronavirus antigen or a nucleic acid that encodes a coronavirus antigen encapsulated in the nanoparticle core.

2 . The SNA of claim 1 , wherein the coronavirus antigen is receptor binding domain (RBD) (SEQ ID NO: 4), S1 subunit of Spike (SEQ ID NO: 5), SARS-COV-2 Spike (SEQ ID NO: 2), a variant of any of the foregoing, or a combination thereof.

3 . The SNA of claim 1 , wherein the coronavirus antigen comprises or consists of a sequence that is at least 80% identical to receptor binding domain (RBD) (SEQ ID NO: 4), S1 subunit of Spike (SEQ ID NO: 5), SARS-COV-2 Spike (SEQ ID NO: 2), SARS-COV-2 surface glycoprotein (SEQ ID NO: 14), SARS-COV-2 RBD (SEQ ID NO: 15), SARS-COV-2 Omicron variant RBD (SEQ ID NO: 16), RBD (SEQ ID NO: 17), or a combination thereof.

4 . The SNA of claim 1 , wherein at least about 0.5 milligram (mg) of the coronavirus antigen is encapsulated in the nanoparticle core per micromole (μmol) of oligonucleotides in the shell of oligonucleotides.

5 . The SNA of claim 4 , wherein about 0.5 mg to about 10 mg of the coronavirus antigen is encapsulated in the nanoparticle core per micromole (μmol) of oligonucleotides in the shell of oligonucleotides.

6 . The SNA of claim 1 , wherein the nanoparticle core is a lipid nanoparticle core.

7 . The SNA of claim 1 , wherein the shell of oligonucleotides comprises DNA, RNA, or a combination thereof.

8 . The SNA of claim 1 , wherein the nanoparticle core comprises DNA, RNA, or a combination thereof encapsulated therein.

9 . The SNA of claim 1 , wherein the ratio of oligonucleotides in the shell of oligonucleotides to the coronavirus antigen encapsulated in the nanoparticle core is about 10:1 to about 70:1 (number of oligonucleotides in the shell of oligonucleotides to the number of coronavirus antigen molecules encapsulated in the nanoparticle core).

10 . The SNA of claim 9 , wherein the ratio of oligonucleotides in the shell of oligonucleotides to the coronavirus antigen encapsulated in the nanoparticle core is about 16:1.

11 . The SNA of claim 9 , wherein the ratio of oligonucleotides in the shell of oligonucleotides to the coronavirus antigen encapsulated in the nanoparticle core is about 32:1.

12 . The SNA of claim 9 , wherein the ratio of oligonucleotides in the shell of oligonucleotides to the coronavirus antigen encapsulated in the nanoparticle core is about 43:1.

13 . The SNA of claim 1 , wherein the shell of oligonucleotides comprises a targeting oligonucleotide, an inhibitory oligonucleotide, or a combination thereof.

14 . The SNA of claim 1 , wherein the immunostimulatory oligonucleotide is a CpG-motif containing oligonucleotide, a double-stranded DNA oligonucleotide, or a single-stranded RNA oligonucleotide.

15 . The SNA of claim 6 , wherein each of the immunostimulatory oligonucleotides is a toll-like receptor (TLR) agonist.

16 . A pharmaceutical formulation comprising the SNA of claim 1 and a pharmaceutically acceptable carrier or diluent.

17 . An antigenic composition comprising the SNA of claim 1 in a pharmaceutically acceptable carrier, diluent, stabilizer, preservative, or adjuvant, wherein the antigenic composition is capable of generating an immune response including antibody generation or a protective immune response in a mammalian subject.

18 . The SNA of claim 6 , wherein the nucleic acid is mRNA.

19 . The SNA of claim 6 , wherein the lipid nanoparticle core comprises an ionizable lipid, a phospholipid, a sterol, and a lipid-polyethylene glycol (lipid-PEG) conjugate.

20 . The SNA of claim 19 , wherein each oligonucleotide in the shell of oligonucleotides is covalently attached to the exterior of the lipid nanoparticle core through the lipid-PEG conjugate.

21 . The SNA of claim 1 , wherein the nanoparticle core is a liposomal core.

22 . The SNA of claim 21 , wherein the liposomal core comprises a plurality of lipid groups.

23 . The SNA of claim 22 , wherein the plurality of lipid groups comprises a lipid selected from the group consisting of the phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine families of lipids.

24 . The SNA of claim 1 , wherein at least one oligonucleotide in the shell of oligonucleotides is attached to the exterior of the liposomal or lipid nanoparticle core through a lipid anchor group.

25 . The SNA of claim 24 , wherein the lipid anchor group is attached to the 5′ end or the 3′ end of the at least one oligonucleotide.

26 . The SNA of claim 24 , wherein the lipid anchor group is tocopherol or cholesterol.

27 . The SNA of claim 1 , wherein the shell of oligonucleotides comprises DNA oligonucleotides and RNA oligonucleotides.

28 . The SNA of claim 1 , wherein the shell of oligonucleotides comprises single-stranded DNA, double-stranded DNA, single-stranded RNA, double-stranded RNA, or a combination thereof.

29 . The SNA of claim 6 , wherein the nanoparticle core comprises single-stranded DNA, double-stranded DNA, single-stranded RNA, double-stranded RNA, or a combination thereof encapsulated therein.

30 . The SNA of claim 1 , wherein the shell of oligonucleotides comprises at least 200 oligonucleotides.

31 . The SNA of claim 1 , wherein the shell of oligonucleotides is attached to the external surface of the nanoparticle core at a surface density of about 2 pmol/cm 2 to about 200 pmol/cm 2 .

32 . The SNA of claim 6 , wherein each oligonucleotide in the shell of oligonucleotides is about 10 to about 50 nucleotides in length.

33 . The SNA of claim 32 , wherein each oligonucleotide in the shell of oligonucleotides is about 20 to about 30 nucleotides in length.

34 . The SNA of claim 6 , wherein diameter of the SNA is about 10 nanometer (nm) to about 150 nm.

35 . The SNA of claim 1 , wherein diameter of the SNA is less than or equal to about 50 nanometers.

36 . The SNA of claim 6 , wherein each oligonucleotide in the shell of oligonucleotides is an immunostimulatory oligonucleotide.

37 . The SNA of claim 15 , wherein the TLR is toll-like receptor 9 (TLR9).

38 . A method of producing an immune response to a coronavirus antigen in a subject, comprising administering to the subject an effective amount of the antigenic composition of claim 17 , thereby producing an immune response to the viral antigen in the subject.

39 . A method of treating a coronavirus infection in a subject in need thereof, comprising administering to the subject an effective amount of the SNA of claim 1 , thereby treating the coronavirus infection in the subject.

40 . The method of claim 38 , wherein the administering is intravenous, intraperitoneal, intranasal, subcutaneous, or intramuscular.

41 . The method of claim 38 , wherein the administering comprises at least one dose of the antigenic composition.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 5, 2024
From: MIRKIN, CHAD A.; TEPLENSKY, MICHELLE HOPE; DISTLER, MAX EVERETT; KUSMIERZ, CAROLINE DANIELLE; CALLMANN, CASSANDRA ELIZABETH
To: NORTHWESTERN UNIVERSITY
Reel/Frame 067915/0622 →
Continuity (3)
Provisional Application 63250908 · Sep 30, 2021
Provisional Application 63160600 · Mar 12, 2021
Related Publication 20220288181A1 · Sep 15, 2022
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