Periodic two and three dimensional nucleic acid structures

• US 6,255,469 B1
• Filed: 05/06/1999
• Issued: 07/03/2001
• Est. Priority Date: 05/06/1998
• Status: Active Grant

• Current Assignee: New York University
• Original Assignee: New York University
• Inventors: Seeman, Nadrian, Winfree, Erik, Liu, Furong, Wenzler Savin, Lisa
• Primary Examiner(s): Brusca, John S.
• Application Number:
  US09/306,405
• Time in Patent Office: 789 Days
• Field of Search: 536/23.1, 536/24.1, 536/24.2, 536/24.5, 536/25.3
• US Class Current: 536/23.1
• CPC Class Codes: C12N 15/1031 mutagenesis by gene assembly, e.g. assembly by oligonucleotide extension PCR

Abstract

Two- and three-dimensional periodic lattices are constructed from repeating units of at least two antiparallel nucleic acid multi-crossover molecules. The repeating units range from single component to multi-component.

Claims

1. A periodic polynucleic acid structure, comprising a lattice of adjacent coplanar repeating units, each repeating unit comprising at least two antiparallel nucleic acid multi-crossover molecules, each of said at least two antiparallel nucleic acid multi-crossover molecules comprising two or more adjacent double helical domains, at least two of said two or more adjacent double helical domains having a first and second cohesive ends, each of said adjacent double helical domains having helix axes in parallel and being connected to adjacent double helical domains at two or more crossover sites, with each antiparallel nucleic acid multi-crossover molecules being connected to an adjacent antiparallel nucleic acid multi-crossover molecule by complementary cohesive ends, thereby forming an extended double helical domain between a first double helical domain of an antiparallel nucleic acid multi-crossover molecule and a second double helical domain of an adjacent antiparallel nucleic acid multi-crossover molecule, wherein a second double helical domain of said antiparallel nucleic acid multi-crossover molecule is not colinear and connectible with a first double helical domain of said adjacent antiparallel nucleic acid crossover molecule to form an extended double helical domain, and wherein each repeating unit is connected to an adjacent repeating unit in the same plane by complementary cohesive ends to form at least one extended double helical domain between adjacent repeating units in the same plane.

2. The periodic polynucleic acid structure according to claim 1, wherein said at least two antiparallel nucleic acid multi-crossover molecules of each repeating unit are coplanar.

3. The periodic polynucleic acid structure according to claim 1, wherein said at least two antiparallel nucleic acid multi-crossover molecules are antiparallel nucleic acid double crossover molecules.

4. The periodic polynucleic acid structure according to claim 1, wherein said at least two antiparallel nucleic acid multi-crossover molecules are antiparallel nucleic acid molecules having three double helical domains with parallel helix axes.

5. The periodic polynucleic acid structure according to claim 1, wherein said repeating units each comprises two different antiparallel nucleic acid multi-crossover molecules.

6. The periodic polynucleic acid structure according to claim 1, wherein said repeating units each comprises four different antiparallel nucleic acid multi-crossover molecules.

7. The periodic polynucleic acid structure according to claim 1, wherein said at least two antiparallel nucleic acid multi-crossover molecules are antiparallel nucleic acid multi-crossover having at least four double helical domains with parallel helix axes.

8. The periodic polynucleic acid structure according to claim 7, wherein one of said at least four double helical domains is a central double helical domain which is centrally located and surrounded by the remaining double helical domains of said at least four double helical domains.

9. The periodic polynucleic acid structure according to claim 7, wherein said at least four double helical domains are arranged with cylic symmetry.

10. The periodic polynucleic acid structure according to claim 7, wherein said at least two antiparallel nucleic acid multi-crossover molecules have four double helical domains with parallel helix axes.

11. The periodic polynucleic acid structure according to claim 7, wherein said at least two antiparallel nucleic acid multi-crossover molecules have six double helical domains with parallel helix axes.

12. The periodic polynucleic acid structure according to claim 1, wherein said lattice is two-dimensional.

13. The periodic polynucleic acid structure according to claim 1, wherein one or more of said at least two antiparallel nucleic acid multi-crossover molecules in each of said repeating units further comprises an additional helical domain whose helix axis is not parallel to the helix axes of said two or more adjacent helical domains, said additional helical domain having a first and second end, said first end of said additional helical domain forms a junction with one of said two or more adjacent helical domains.

14. The periodic polynucleic acid structure according to claim 1, wherein said lattice is extended into a third dimension.

15. The periodic polynucleic acid structure according to claim 14, wherein one or more of said at least two antiparallel nucleic acid multi-crossover molecules in each of said adjacent coplanar repeating units further comprises an additional helical domain whose helix axis is not parallel to the helix axes of said two or more adjacent helical domains, said additional helical domain having a first and second, wherein said first end of said additional helical domain forms a junction with one of said two or more adjacent helical domains and said second end of said additional helical domain is connected by a complementary cohesive end to a corresponding additional helical domain of an antiparallel nucleic acid multi-crossover molecule in a repeating unit disposed in a plane parallel to a plane formed of said at least two antiparallel nucleic acid multi-crossover molecules in each of said repeating units.

16. The periodic polynucleic acid structure according to claim 1, wherein said periodic polynucleic acid structure is self-assembling.

17. A method for producing a periodic polynucleic acid structure according to claim 1, comprising the steps of:

(a) synthesizing at least four single-stranded polynucleotides, each being self-complementary and/or complementary to another single-stranded polynucleotide, wherein the at least four single-stranded polynucleotides are capable of hybridizing together to form the at least two antiparallel nucleic acid multi-crossover molecules of each repeating unit;

(b) mixing the at least four single-stranded polynucleotides to form a mixture and heat denaturing the mixture;

(c) annealing the mixture of at least four single-stranded polynucleotides to form a lattice of repeating units of at least two adjacent antiparallel nucleic acid multi-crossover molecules; and

(d) ligating complementary cohesive ends between adjacent antiparallel nucleic acid multi-crossover molecules to produce the periodic polynucleic acid structure.