Self-assembly of nucleic acid nanostructures
The invention involves the synthesis of nucleic acid structures of controlled size and shape and comprised of a plurality of oligonucleotides. The structures are formed, at least in part, by the self-assembly of single-stranded oligonucleotides. The location of each oligonucleotide in the resultant structure is known. Accordingly, the structures may be modified with specificity.
1. A three-dimensional nucleic acid structure comprising
a plurality of 10 or more single-stranded oligonucleotides, wherein each of the single-stranded oligonucleotides has a length of 28 nucleotides to 36 nucleotides and forms two adjacent antiparallel double helices connected to each other by a single phosphate bond, wherein one of the double helices comprises two adjacent nucleotide domains and the other of the double helices comprises two adjacent nucleotide domains, and each nucleotide domain of a single-stranded oligonucleotide of the plurality is complementary to and binds to a nucleotide domain of another single-stranded oligonucleotide of the plurality to form a 90° dihedral angle.
2. The nucleic acid structure of claim 1 , wherein the nucleotide domains of the double helices are of equal nucleotide length.
3. The nucleic acid structure of claim 1 , wherein each domain is 8 nucleotides in length.
4. The nucleic acid structure of claim 1 , wherein the structure further comprises single-stranded 2-domain oligonucleotides.
5. The nucleic acid structure of claim 1 , wherein the oligonucleotides are DNA oligonucleotides.
6. The nucleic acid structure of claim 1 , wherein the DNA oligonucleotides are L-DNA oligonucleotides.
7. The nucleic acid structure of claim 1 , wherein the single-stranded oligonucleotides of the plurality are crosslinked to each other.
8. The nucleic acid structure of claim 1 , wherein the nucleic acid structure comprises 100, 500, or 1000 of the single-stranded oligonucleotides.
9. The nucleic acid structure of claim 1 , wherein the structure is a cuboid structure, a cylindrical structure, a sheet, a honeycomb structure, or a hexagonal lattice structure.
10. The nucleic acid structure of claim 1 , wherein the structure is a Z-crystal, a ZX-crystal, a Y-crystal, an X-crystal, an XY-crystal, or a ZXY crystal.
11. A method of producing a three-dimensional nucleic acid nanostructure, comprising:
annealing in a vessel a plurality of 10 or more single-stranded oligonucleotides, wherein each of the single-stranded oligonucleotides has a length of 28 nucleotides to 36 nucleotides and forms two adjacent antiparallel double helices connected to each other by a single phosphate bond, wherein one of the double helices comprises two nucleotide domains and the other of the double helices comprises two nucleotide domains, and each nucleotide domain of a single-stranded oligonucleotide of the plurality is complementary to and binds to a nucleotide domain of another single-stranded oligonucleotide of the plurality to form a 90° dihedral angle, thereby producing a three-dimensional nucleic acid nanostructure.
12. The method of claim 11 , wherein the single-stranded oligonucleotides are present at equal molar concentrations.
13. The method of claim 11 , wherein annealing occurs through a temperature transition over a period of time.
14. The method of claim 13 , wherein the temperature transition is a change in temperature from an elevated temperature to room temperature.
15. The method of claim 14 , wherein the temperature transition is a change in temperature from 90° C. to room temperature.
16. The method of claim 11 , wherein the annealing occurs over a period of 12-24 hours.
17. The method of claim 11 , wherein each domain is 8 nucleotides in length.
18. The method of claim 11 , wherein the single-stranded oligonucleotides are DNA oligonucleotides.
19. The method of claim 18 , wherein the single-stranded DNA oligonucleotides are L-DNA oligonucleotides.