Lipid-coated nucleic acid nanostructures of defined shape

Patent metadata

Field	Value
Publication number	US-9717685-B2
Application number	US-201314387645-A
Country	US
Kind code	B2
Filing date	Mar 13, 2013
Priority date	Mar 26, 2012
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

Abstract

The invention provides nanoparticles containing a nucleic acid nanostructure, of defined shape and size, linked to a hydrophobic moiety and coated by lipids, compositions comprising the nanoparticles, and methods of producing and methods of using the nanoparticles.

First claim

What is claimed is:

1. A nanoparticle comprising a nucleic acid nanostructure core and a lipid coating, wherein the nucleic acid nanostructure has a void volume of at least 25% and is attached to a hydrophobic moiety through
(a) a single-stranded oligonucleotide conjugate comprising the hydrophobic moiety, or
(b) a binding pair, one member of which is attached to the nanostructure and one member of which is attached to the hydrophobic moiety,
wherein the hydrophobic moiety is in contact with the lipid coating.

2. The nanoparticle of claim 1 , wherein the lipid coating is a lipid bilayer having an interior layer, a transmembrane region, and an exterior layer.

3. The nanoparticle of claim 2 , wherein the hydrophobic moiety is positioned within the transmembrane region of the lipid bilayer, or extends through the lipid bilayer and is positioned exterior to the nanoparticle.

4. The nanoparticle of claim 1 , wherein the hydrophobic moiety is a lipid, a peptide, or a surfactant.

5. The nanoparticle of claim 1 , wherein the oligonucleotide conjugate is hybridized to the nucleic acid nanostructure, or is hybridized to a single-stranded nucleic acid handle that is attached to the nucleic acid nanostructure.

6. The nanoparticle of claim 5 , wherein the single-stranded nucleic acid handle is covalently attached to the nucleic acid nanostructure.

7. The nanoparticle of claim 1 , wherein the binding pair is an avidin-biotin binding pair, an antigen-antibody binding pair or a receptor-ligand binding pair.

8. The nanoparticle of claim 7 , wherein the binding pair is biotin and streptavidin.

9. The nanoparticle of claim 1 , wherein the lipid coating is heterogeneous.

10. The nanoparticle of claim 1 , wherein the lipid coating comprises a phospholipid, an aminolipid, a sphingolipid, or a combination thereof.

11. The nanoparticle of claim 1 , wherein the lipid coating comprises cholesterol, sphingomyelin, cardiolipin, or a combination thereof.

12. The nanoparticle of claim 1 , wherein the lipid coating comprises a neutral lipid or a cationic lipid.

13. The nanoparticle of claim 12 , wherein the lipid coating comprises a neutral lipid that is uncharged or is zwitterionic.

14. The nanoparticle of claim 1 , wherein the lipid coating has an overall neutral or positive charge.

15. The nanoparticle of claim 1 , wherein the shape of the lipid coating is substantially the same as the shape of the nucleic acid nanostructure.

16. The nanoparticle of claim 1 , wherein the defined shape is selected from the group consisting of: a hemi-sphere, a cube, a cuboidal, a tetrahedron, a cylinder, a cone, an octahedron, a prism, a sphere, a pyramid, a dodecahedron, a tube, and an irregular shape.

17. The nanoparticle of claim 1 , wherein the nanoparticle may have a cross section length of less than 1000 nanometers.

18. The nanoparticle of claim 1 , further comprising an agent, optionally attached to the nanostructure core, or encapsulated within a volume created by the lipid coating.

19. The nanoparticle of claim 18 , wherein an agent is attached to the hydrophobic moiety.

20. The nanoparticle of claim 18 , wherein the agent is a therapeutic agent, a prophylactic agent, or a diagnostic agent.

21. The nanoparticle of claim 1 , wherein the nanoparticle does not comprise an agent.

22. A composition comprising the nanoparticle of claim 1 and a carrier or excipient.

23. The nanoparticle of claim 1 , wherein the nucleic acid nanostructure is three-dimensional.

24. The nanoparticle of claim 1 , wherein the nucleic acid nanostructure comprises a long nucleic acid strand hybridized to a plurality of nucleic acid strands that are shorter than the long nucleic acid strand.

25. The nanoparticle of claim 1 , wherein the nucleic acid nanostructure comprises a plurality of nucleic acid strands hybridized to each other, each nucleic acid strand having a length of less than 200 nm.

26. The nanoparticle of claim 1 , wherein the nanoparticle has a void volume of at least 50%.

27. The nanoparticle of claim 26 , wherein the nanoparticle has a void volume of at least 75%.

28. A nanoparticle comprising a nucleic acid nanostructure core and a lipid bilayer coating comprising an interior layer, a transmembrane region, and an exterior layer coating, wherein the nucleic acid nanostructure is attached to a hydrophobic moiety through a single-stranded oligonucleotide conjugate comprising the hydrophobic moiety, wherein the hydrophobic moiety is in contact with the lipid bilayer coating.

29. The nanoparticle of claim 28 , wherein the hydrophobic moiety is positioned within the transmembrane region of the lipid bilayer, or extends through the lipid bilayer and is positioned exterior to the nanoparticle.

30. A nanoparticle comprising a nucleic acid nanostructure core and a lipid bilayer coating comprising an interior layer, a transmembrane region, and an exterior layer coating, wherein the nucleic acid nanostructure is attached to a hydrophobic moiety through a binding pair, one member of which is attached to the nanostructure and one member of which is attached to the hydrophobic moiety, wherein the hydrophobic moiety is in contact with the lipid bilayer coating.

31. The nanoparticle of claim 30 , wherein the hydrophobic moiety is positioned within the transmembrane region of the lipid bilayer, or extends through the lipid bilayer and is positioned exterior to the nanoparticle.

Assignees

• Harvard College

Inventors

• Shih William M
• Perrault Steven

Classifications

• B82Y40/00

  Manufacture or treatment of nanostructures · CPC title

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61K9/127 Primary

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• C12N15/88

  using microencapsulation, e.g. using {amphiphile} liposome vesicle · CPC title