Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-05-06
2001-07-03
Brusca, John S. (Department: 1631)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S025300
Reexamination Certificate
active
06255469
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to two-dimensional and three-dimensional polynucleic acid nanostructures which are periodic and thereby translationally symmetrical.
2. Description of The Related Art
A key aim of biotechnology and nanotechnology (Feynman et al, 1961, and Drexler, 1981) is a rational approach to the construction of new biomaterials, including individual geometrical objects and nanomechanical devices, and extended constructions, particularly periodic matter with control of the molecule architecture such that it would permit the fabrication of intricate arrangements of atoms to serve many practical purposes (Robinson et al, 1987; Seeman, 1991a; Seeman, 1991b). The informational macromolecules of biological systems, proteins and nucleic acids, are believed to have the potential to serve as building blocks for these constructions, because they are used for similar purposes in the cell. For instance, nanometer-scale circuitry and robotics could accomplish many tasks that are impossible today. One can envision improvements in the storage and retrieval of information, directed attacks on the molecular basis of medical problems, and the assembly of very smart materials as possible end products of the ability to control the structure of matter on the nanometer scale.
There are at least three key elements necessary for the control of three-dimensional structure in molecular construction that involves the high symmetry associated with crystals: (1) the predictable specificity of intermolecular interactions between components; (2) the structural predictability of intermolecular products; and (3) the structural rigidity of the components (Liu et al, 1994). DNA branched junctions are excellent building blocks from the standpoint of the first two requirements, which are also needed for the construction of individual objects, because (1) ligation directed by Watson-Crick base pairing between sticky-ended molecules has been used successfully to direct intermolecular specificity since the early 1970's (Cohen et al, 1973); and (2) the ligated product is double helical B-DNA, whose local structural parameters are well-known (Arnott et al, 1973).
The key problem in working with branched DNA as a construction medium is that branched junctions have been shown to be extremely flexible molecules (Ma et al, 1986; Petrillo et al, 1988). The ligation of 3-arm and 4-arm DNA branched junctions leads to many different cyclic products, suggesting that the angles between the arms of the junctions vary on the ligation time-scale; these angles are analogous to valence angles around individual atoms. Likewise, a 5-arm DNA branched junction has been shown to have no well-defined structure, and a 6-arm DNA branched junction has only a single preferred stacking domain (Wang et al, Biochem. 30:5667-5674). Leontis and his colleagues have shown that a three-arm branched junction containing a loop of two deoxythymidine nucleotides has a preferred stacking direction (Leontis et al, 1991) and ligation along this direction shows a lower propensity to cyclization (21.3%) than other directions (Liu et al, 1994), but it is not possible to treat the stacking domain in the Leontisian junction as a rigid component (Qi et al, 1996).
To overcome the problem of branched DNA being extremely flexible and therefore unsuitable from the standpoint of structural rigidity of the components as the third key element, DNA structures that fail to cyclize significantly in the course of ligation reactions (a measure of the rigidity of the DNA) were sought by the present inventors. DNA double crossover molecules, which are model systems for structures proposed to be involved in genetic recombination initiated by double strand breaks (Sun et al, 1991; Thaler et al, 22:169-197, 1988), as well as meiotic recombination (Schwacha et al, 1995), were explored with respect to the structural features of these molecules, and a laboratory of the inventors has shown that there are five different isomers of double crossover molecules (Fu et al, 1993). Double crossover molecules were used in the laboratory of the present inventor to establish the sign of the crossover node in the Holliday junction (Fu et al, 1994b), to construct symmetric immobile branched junctions (Zhang et al, 1994b), and to examine the effect of domain orientation on cleavage by the Holliday junction resolvase, endonuclease VII (Fu et al, 1994a). The helical domains were found to be parallel in three of the five isomers, and antiparallel in the other two. Those with parallel domains are not as well-behaved as those with antiparallel domains (Fu et al, 1993).
A laboratory of the present inventors reported the design of geometrical objects and lattices composed of rigid motifs, such as triangles and deltahedra, etc., formed from antiparallel nucleic acid double crossover molecules (Li et al, 1996; WO 97/41142). These findings stimulated a theoretical proposal to use aperiodic two-dimensional (2-D) lattices of double crossover molecules (Winfree, 1996) for DNA-based computation (Adleman, 1994). In the mathematical theory of tiling (Grunbaum et al, 1986), rectangular tiles with programmable interactions, known as Wang tiles, can be designed so that their assembly must mimic the operation of a chosen Turing Machine (H. Wang, 1963). Double crossover molecules acting as molecular Wang tiles could self-assemble to perform desired computations (Winfree, 1996).
Citation of any document herein is not intended as an admission that such document is pertinent prior art, or considered material to the patentability of any claim of the present application. Any statement as to content or a date of any document is based on the information available to applicant at the time of filing and does not constitute an admission as to the correctness of such a statement.
SUMMARY OF THE INVENTION
The present invention provides a two-dimensional periodic lattice formed of coplanar repeating units, each of which is composed of at least two antiparallel nucleic acid multi-crossover molecules. Anti-parallel nucleic acid multi-crossover molecules are connected to an adjacent antiparallel nucleic acid multi-crossover molecule either within a repeating unit or between adjacent repeating units by complementary cohesive ends. The at least two antiparallel nucleic acid crossover molecules in a repeating unit are either the same antiparallel nucleic acid multi-crossover molecule or a multi-component arrangement of different antiparallel nucleic acid multi-crossover molecules.
The present invention also provides for a three-dimensional periodic lattice which may be formed as an extension of the two-dimensional period lattice into a third dimension, such as by interconnecting adjacent two-dimensional lattices by joining together antiparallel nucleic acid multi-crossover molecules in adjacent planes. The present invention provides antiparallel nucleic acid crossover molecules with a helical arm or domain which projects out of the plane of a two-dimensional lattice to connect by complementary cohesive ends to a corresponding helical arm from an adjacent two-dimensional lattice and produce a stacking of two-dimensional lattices.
REFERENCES:
patent: 6072044 (2000-06-01), Seeman et al.
Winfree et al ., “On the Computational Power of DNA Annealing and Ligation”,DIAMACS Series in Discrete Mathematics and Theoretical Computers Science, vol. 27, pp. 199-221, (1995).
Li et al., “Antiparallel DNA Double Crossover Molecules As Components for Nanoconstruction”,Journal of the American Chemical Society,vol. 118, No. 26, pp. 6131-6140, (1996).
Liu Furong
Seeman Nadrian
Wenzler Savin Lisa
Winfree Erik
Browdy & Neimark
Brusca John S.
New York University
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