WO2009093558A1 - Élément de construction d'acide nucléique, produit de construction d'acide nucléique utilisant celui-ci et procédé de fabrication du produit de construction d'acide nucléique - Google Patents

Élément de construction d'acide nucléique, produit de construction d'acide nucléique utilisant celui-ci et procédé de fabrication du produit de construction d'acide nucléique Download PDF

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WO2009093558A1
WO2009093558A1 PCT/JP2009/050720 JP2009050720W WO2009093558A1 WO 2009093558 A1 WO2009093558 A1 WO 2009093558A1 JP 2009050720 W JP2009050720 W JP 2009050720W WO 2009093558 A1 WO2009093558 A1 WO 2009093558A1
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nucleic acid
base sequence
acid structure
complementary
double helix
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PCT/JP2009/050720
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English (en)
Japanese (ja)
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Satoshi Murata
Shogo Hamada
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Tokyo Institute Of Technology
Hayashinaka, Teruo
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA

Definitions

  • the crossover structural unit which is a branched structure of this DNA double helix, is Holday. It was developed from a structure called Junction that appears at the time of homologous recombination of a gene in vivo (for example, see Non-Patent Document 4).
  • this crossover structural unit used in a nanonucleic acid structure forms a form in which two DNA double helices are arranged in parallel as shown in FIG.
  • a double crossover molecule as shown in FIGS. 16A and 16B, in which the structure is stabilized by combining two or more thereof, is widely used as a basic unit (for example, Non-Patent Document 6). reference).
  • the method for producing a nucleic acid structure according to the present invention comprises a double helix structure with a pair of nucleotide chains having a base sequence that is non-complementary to the other nucleotide chain at a predetermined position of the non-terminal part of one nucleotide chain.
  • a nucleotide chain having a free-end base sequence complementary to the base sequence and the nucleic acid molecule are hydrogen-bonded between the complementary base sequences.
  • the nucleic acid structure according to the present invention is configured by combining a plurality of repeating structures, and the plurality of repeating structures have a planar structure and a double helix simple structure,
  • the nucleotide chain of one of the repeating structures has a base sequence complementary to the nucleotide sequence of the nucleotide chain of another adjacent repeating structure.
  • FIG. 1 It is a schematic diagram of a DNA double helix structure. It is a figure for demonstrating the phase difference in the main groove side and subgroove side of a DNA double helix structure. It is the schematic of the nucleic acid structure which the base sequence of the oligonucleotide used in order to form the nucleic acid structure which has a branched structure, and the base sequence can form theoretically. It is the electrophoresis result figure which electrophoresed the reaction solution made to react using the oligonucleotide which has a base sequence shown in FIG.
  • the present invention is particularly based on nucleic acid structures formed by self-assembly of oligonucleotides composed of artificially designed and synthesized sugars, phosphates, and bases, and this suitable design.
  • the present invention relates to a nanometer-scale nucleic acid structure produced using the prepared nucleic acid structure as a structural unit.
  • a complementary base sequence refers to a base sequence in a binding relationship that can form a base pair based on Watson-Crick complementarity.
  • FIG. 1 is a schematic diagram three-dimensionally showing the nucleic acid structure according to the present embodiment. As shown in FIG. 1, this nucleic acid structure is bent at any phase of the double helix of nucleic acid so that the double helix is branched in the vertical direction, and another double helix is connected to the bent portion. Thus, a branched structure is formed.
  • nucleic acid molecules such as DNA, RNA, and PNA can be used as the nucleic acid.
  • DNA used as a nucleic acid molecule
  • PNA PNA
  • an example in which DNA is used as a nucleic acid molecule will be described specifically, but the nucleic acid molecule used in the nucleic acid structure according to the present embodiment is not limited to DNA.
  • the nucleic acid structure according to the present embodiment has a double helical structure by forming a hydrogen bond between the bases having the complementary binding relationship between the first oligonucleotide 11 and the second oligonucleotide 12.
  • a second nucleic acid having a double helical structure by generating a first nucleic acid molecule and forming a hydrogen bond between bases having a complementary relationship between the third oligonucleotide 13 and the fourth oligonucleotide 14 A molecule is generated, and then the free-end base sequence of the first oligonucleotide 11 constituting the first nucleic acid molecule and the third oligonucleotide 13 constituting the second nucleic acid molecule have at the non-terminal part. It is formed by hydrogen bonding between the base sequence having a complementary relationship with the free end base sequence.
  • the oligonucleotide is sequenced in consideration of the base sequence length of the binding portion. Make a decision. This is because the longer the base sequence length of the oligonucleotide to be hybridized, the higher the temperature environment, the higher the temperature environment, and the shorter the base sequence length, the lower the temperature environment, the lower the temperature environment. This is for self-assembly.
  • the first duplex ( ⁇ ) and the third oligonucleotide ( ⁇ +) have a first duplex as compared to the base sequence length of each oligonucleotide. Since the base sequence length that becomes the connecting part between the helical DNA molecule and the second double helical DNA molecule is designed to be extremely short, the nucleic acid structure is self-assembled by controlling the temperature from a high temperature to a low temperature. By forming, each DNA molecule is first formed, and then, the formed DNA molecules are connected by hydrogen bonding to construct a T-shaped nucleic acid structure. As a result, hydrogen bonds are formed at unintended sites, and an unintended nucleic acid structure is not formed.
  • nucleotide sequence determination of the oligonucleotide for forming the T-shaped nucleic acid structure considering that the double helix of DNA bends at an appropriate site, Comprehensive possible hybridization between all base sequences used, considering information on base sequence length to form hydrogen bonds in complementary base sequence parts in the intended order under appropriate temperature control Except for the case where the desired structure is formed, the sequence is determined so that unintentional double helix formation does not occur between the base sequences at high temperatures.
  • an oligonucleotide having a free-end base sequence consisting of 5 bases at the 5 ′ end and an oligonucleotide having a base sequence that forms a hydrogen bond complementary to the oligonucleotide form a double-stranded DNA molecule.
  • the nucleotide sequence is determined so that the oligonucleotide having the nucleotide sequence that forms a bond forms a double helix DNA molecule.
  • a T-shaped nucleic acid structure having a structure branched in the vertical direction by self-assembling four kinds of oligonucleotides synthesized based on these designs from a high temperature to a low temperature under temperature control Can be formed.
  • this double helix structure is assumed to be a cylindrical shape, let us consider branching and extending the double helix in a direction perpendicular to the cylindrical shape. Since the value of the diameter of the DNA double helix structure is 2.19 nm as described above, from the calculation formula (2) below, 2.19 / 0.34 ⁇ 6.44 (bp) (2) That is, the length of about 6 to 7 bp corresponds to the length of the diameter of the DNA double helix structure, in other words, the length between opposing complementary base pairs, and therefore, the distance of 6 or 7 bp.
  • the nucleic acid molecule is not limited to DNA, and the interval formed at the connecting portion is limited to the interval corresponding to the main groove side 6 or 7 bp. It is not something. That is, the nucleic acid structure according to this embodiment can be formed using nucleic acid molecules such as RNA and PNA.
  • the nucleic acid structure according to this embodiment can be formed using nucleic acid molecules such as RNA and PNA.
  • the nucleic acid structure according to this embodiment can be formed using nucleic acid molecules such as RNA and PNA.
  • the length of the diameter of the double helix in other words, the length between the opposing complementary base pairs.
  • T-shaped nucleic acid structure Even within the unit, there is a difference in the order of hybridization between the oligonucleotides forming the unit structure.
  • two double helices constituting a T-shaped nucleic acid structure are first formed by hydrogen bonding between complementary base sequences between oligonucleotides, followed by Two double helices are hybridized at a complementary base sequence portion consisting of 5 bases to form a T-shaped nucleic acid structure as a unit structure.
  • bonding between units is started under a low temperature environment, and a plurality of units are hydrogen-bonded. As a result, a nanonucleic acid structure is formed.
  • the number of types of oligonucleotides used is not limited, and the nucleic acid structure may be prepared by annealing four kinds of oligonucleotides. Alternatively, a nucleic acid structure may be prepared by reacting two kinds of oligonucleotides.
  • This ladder-type structure is based on a shape in which double helix DNA is vertically connected between double helix DNAs arranged in parallel, and is produced by forming a branched structure in the same phase of the double helix structure. can do.
  • a ladder-type structure having a structure as a repeating structure can be created.
  • FIG. 10 is a diagram schematically showing a specific unit structure of a nano-nucleic acid structure and a partial structure of a planar structure that is a nano-nucleic acid structure that is produced using the unit structure as a repetitive structure.
  • a structure in which two T-shaped nucleic acid structures are combined in opposite directions is determined as a unit structure, and a plurality of unit structures are connected as a repeating structure. It is a lattice structure formed by making it.
  • the numbers described in the structure shown in FIG. 10 indicate the number of base pairs (bp), and + and ⁇ indicate the arrangement site of the oligonucleotide having the base sequence shown below.
  • this oligonucleotide As a method for forming a planar structure using this oligonucleotide, it can be prepared by a one-pot annealing method, similarly to the method for forming a ladder structure described in the first embodiment.
  • nucleic acid to be used is not limited to DNA, and it goes without saying that application to functional nanodevices is possible even when RNA, PNA, or the like is used as the nucleic acid.
  • nucleic acid is not limited to DNA, and a nucleic acid such as RNA or PNA may be used.
  • the nucleic acid structure and the nano nucleic acid structure according to the present embodiment may be formed by combining different nucleic acids such as RNA, DNA and PNA and hybridizing them.
  • the nucleic acid structure is configured by combining a plurality of repetitive structures.
  • the plurality of repetitive structures have a planar structure and a double helix single structure, and one of the repetitive structures is a repetitive structure.
  • the nucleotide chain has a base sequence complementary to the nucleotide sequence of the nucleotide chain of another adjacent repeating structure.
  • a preferable range of the concentration of the cation having a valence of 2 or more will be described.
  • substrate adsorption limited to mica will be described.
  • the concentration of the cation having a valence of 2 or more is desirably in the range of 2 mM to 1 M.
  • Mg 2+ ions it is known that adsorption occurs if it is about 1 M or less.
  • the lower limit varies depending on the concentration of monovalent ions such as Na + in the solution, and the lower the monovalent ion concentration is known to cause adsorption at lower concentrations. I have confirmed.
  • the two base sequences (SEQ ID NOs: 14 and 15) shown in (V) below are designed so that hybridization occurs in the intended order by determining the unit structure that becomes the repetitive structure and examining the phase.
  • the nucleotide sequence of the oligonucleotide The base sequence of this oligonucleotide shows the base sequence in the direction from the 5 'end to the 3' end.
  • FIG. 18 (a3) is an atomic force microscope (AFM) observation image of a ladder structure specifically manufactured by the above operation.
  • AFM atomic force microscope
  • Example 5 The formation operation and confirmation observation of this ladder-shaped nucleic acid structure by a one-pot annealing method were carried out by the following procedure using a method different from Example 4.
  • each oligonucleotide synthesized by determining a base sequence by a program based on the above-described knowledge is dissolved in TAE buffer (1 ⁇ TAE / Mg 2+ (12.5 mM)) so as to have a concentration of 0.1 ⁇ M.
  • the oligonucleotide solution was purified.
  • each of the solutions was dispensed, and all the dispensed solutions were mixed in equal amounts in one reaction tube to purify the oligonucleotide mixed solution.
  • mica pieces manufactured by Niraco, natural mica (muscovite)
  • the solution volume was 200 ⁇ l so that the entire mica piece could touch the solution.
  • the two base sequences shown in (VI) below are designed so that hybridization occurs in the intended order by determining the unit structure to be a repetitive structure and examining the phase.
  • the nucleotide sequence of the oligonucleotide The base sequence of this oligonucleotide shows the base sequence in the direction from the 5 'end to the 3' end.
  • both sequences have a complementary sequence of the base sequence that cannot form a complementary hydrogen bond in the + sequence of the-sequence if it is a + sequence, and in the case of a + sequence. Does not form hydrogen bonds at this stage. Therefore, double-stranded DNA bends at two parts of the base sequence (+ CGACAC in the sequence, ACTGCA in the sequence) that cannot form complementary hydrogen bonds inside the sequence, and a double-shaped structure Will come to form.
  • the base sequences that have not undergone hydrogen bonding function as sticky ends and hydrogen bond.
  • the X portion and the Y portion shown in FIG. 19 (b1) and the X ′ portion and the Y ′ portion are designed to have complementary sequences. As a result, after cooling, the ladder type shown in FIG. 19 (b2) is obtained. A structure is obtained.
  • FIG. 20 (b3) is an atomic force microscope (AFM) observation image of the nucleic acid structure specifically produced by the above operation.
  • the method for the atomic force microscope observation of the nucleic acid structure is the same as in Example 4.
  • Example 7 The formation operation and confirmation observation of this ladder-shaped nucleic acid structure by a one-pot annealing method were carried out by the following procedure using a method different from that in Example 6.
  • FIG. 20 (b4, b5) is an atomic force microscope (AFM) observation image of the nucleic acid structure specifically produced by the above operation.
  • the method for the atomic force microscope observation of the nucleic acid structure is the same as in Example 5.
  • the structure length is significantly increased by the growth of the substrate, and it is clear that the structures are aligned on the substrate.
  • the phenomenon that the structures are aligned is thought to be due to the fact that it is desirable to adsorb as much DNA as possible through counter ions in order to cancel the charge of the substrate.
  • FIG. 21 is a diagram schematically showing a part of the structure of a nucleic acid structure which is a specific nucleic acid structure unit structure (c1) and a nucleic acid structure (c2) produced by repeating the unit structure as a repetitive structure. It is.
  • the nucleic acid structure according to this embodiment is formed by connecting a plurality of T-shaped nucleic acid structures as unit structures and connecting a plurality of T-shaped nucleic acid structures as repeating structures. .
  • the numbers described in the structure shown in FIG. 21 indicate the number of base pairs (bp).
  • both sequences have a complementary sequence of a base sequence that cannot form a complementary hydrogen bond inside the + sequence if it is a + sequence, or if it is a ⁇ sequence, on the 5 ′ end side. Does not form hydrogen bonds at this stage. Therefore, double-stranded DNA is folded at two parts of the base sequence (+ GGGCT in the sequence, -CGTCG in the sequence) that cannot form a complementary hydrogen bond inside the sequence, and a double-shaped structure Will come to form.
  • the base sequences that have not undergone hydrogen bonding function as sticky ends and hydrogen bond.
  • the X portion and the Y portion shown in FIG. 21 (c1) and the X ′ portion and the Y ′ portion are designed to have complementary sequences.
  • the planar type shown in FIG. 21 (c2) is obtained. A structure is obtained.
  • the above-described array 18 is replaced with 20 and the array 19 is replaced with 21.
  • the array 18 is replaced with 22 and the array 19 is replaced with 23.
  • the base sequences that cannot form complementary hydrogen bonds within the sequence are the GGGCT in the + sequence and the CGTCG in the ⁇ sequence in the case of 20, 21 respectively, and the + sequence in the case of 22, 23 Within the CCACA and-within the sequence ATCCG.
  • Example 9 The formation procedure and confirmation observation of this nucleic acid structure by a one-pot annealing method were carried out by the following procedure using a method different from that in Example 8.
  • FIG. 22 (c4, c5) is an atomic force microscope (AFM) observation image of the nucleic acid structure specifically produced by the above operation.
  • the method for the atomic force microscope observation of the nucleic acid structure is the same as in Example 5.
  • Example 8 As is apparent from the AFM observation image of FIG. 22 (c4, c5), the tube-like growth was shown in Example 8, but in Example 9, it grew in a planar shape due to the growth effect on the substrate. Yes.
  • a planar single crystal structure on the order of ⁇ m covers the entire surface of the substrate. Since this single crystal region can be expanded by devising the growth process, large-scale crystal growth can be realized.
  • FIG. 23 is a diagram schematically showing a part of the structure of a nucleic acid structure which is a specific nucleic acid structure unit structure (d1) and a nucleic acid structure (d2) which is produced by repeating the unit structure as a repetitive structure. It is.
  • the nucleic acid structure according to this embodiment is formed by using a T-shaped nucleic acid structure as a unit structure and connecting a plurality of the T-shaped nucleic acid structures as repeating structures. . Note that the numbers described in the structure shown in FIG. 23 indicate the number of base pairs (bp).
  • Example 10 The formation operation and confirmation observation of this nucleic acid structure by the one-pot annealing method were performed according to the following procedure.
  • Example 10 As is apparent from the AFM observation image of FIG. 24 (d4, d5), almost no growth was observed in Example 10, but in Example 11, a planar structure can be produced by growing on the substrate. it can.
  • the sequence 26 having the + sequence and the sequence 27 having the ⁇ sequence form a hydrogen bond at a complementary base sequence portion at a high temperature to form a double helix DNA.
  • both of these sequences have two base sequences that cannot form complementary hydrogen bonds (+ AAGCG inside the sequence, -GTGGA inside the -sequence), and in this base sequence part,
  • the corresponding sequence forming the base pair does not form a hydrogen bond, skips the base sequence having no complementary binding relationship, and continues to form a hydrogen bond with the base portion having the next complementary binding relationship. .
  • both sequences have a complementary sequence of the base sequence that cannot form a complementary hydrogen bond in the + sequence of the-sequence if it is a + sequence, and in the case of a + sequence. Does not form hydrogen bonds at this stage. Therefore, double-stranded DNA is folded at two parts of the base sequence (+ AAGCG in the sequence, GTGGA in the sequence) that cannot form a complementary hydrogen bond inside the sequence, and a double-shaped structure Will come to form.
  • the base sequences that have not undergone hydrogen bonding function as sticky ends and hydrogen bond.
  • the X portion and the Y portion shown in FIG. 25 (e1) and the X ′ portion and the Y ′ portion are designed to have complementary sequences.
  • the two-dimensional portion shown in FIG. 25 (e2) is obtained.
  • a polar coordinate structure is obtained.
  • FIG. 26 is an atomic force microscope (AFM) observation image of the nucleic acid structure specifically produced by the above operation.
  • the method for the atomic force microscope observation of the nucleic acid structure is the same as in Example 5.
  • ⁇ Plane structure (3)> (Comparative Example 1)
  • the basic structure of the repetitive structure will be described with reference to FIGS.
  • the basic structure is composed of eight single-stranded DNAs a to h in FIG. After the six DNA molecules c to h in FIG. 28 are combined to form a hexamer, the two DNA molecules a and b connect the hexamers to each other to form a planar structure as shown in FIG. Form.
  • the conditions for producing the nucleic acid structure will be described. Although it is almost the same as the conditions prepared in Comparative Example 1, this time, since a DNA nucleic acid structure is directly formed on the substrate, a mica substrate having a negative surface charge is placed in the same tube, unlike the conventional annealing of only the sample solution. Was immersed in the sample solution for annealing.
  • the substrate mica (mica) was used, and the size was about 5 mm ⁇ 10 mm, and the size fits in the used tube. Since the amount of the sample solution also needs to be in a state in which the substrate is sufficiently immersed in the solution, the amount of the sample solution was twice the amount of the sample (100 ⁇ l) in the free solution of Comparative Example 1. Specifically, the sample amount was 200 ⁇ l, and the concentration of each DNA molecule was equimolar conditions of 0.04 ⁇ M. The concentration is the same as that in the free solution of Comparative Example 1.
  • the basic structure of the repetitive structure will be described with reference to FIGS.
  • the basic structure is composed of six single-stranded DNAs a to f in FIG. After the DNA molecules a to f in FIG. 34 are bonded to form a hexamer, the hexamers are directly bonded to each other at the sticky end portion on the side located outside the structure, thereby forming a planar structure as shown in FIG. Form.
  • the conditions for producing the nucleic acid structure will be described. Although it is almost the same as the conditions prepared in Comparative Example 2, this time, since a DNA nanostructure is directly formed on a substrate, a mica substrate having a negative surface charge is placed in the same tube unlike conventional annealing of only a sample solution. Was immersed in the sample solution for annealing.
  • the substrate mica (mica) was used, and the size was about 5 mm ⁇ 10 mm, and the size fits in the used tube. Since the amount of the sample solution also needs to be in a state in which the substrate is sufficiently immersed in the solution, the amount was twice as much as the sample amount (100 ⁇ l) in the free solution. Specifically, the sample amount was 200 ⁇ l, and the concentration of each DNA molecule was 0.01 ⁇ M. The concentration is the same as that in Comparative Example 2 when prepared in a free solution.
  • each single-stranded DNA has two bases of thymine (T) at a position corresponding to a corner when taking a cross shape. Since this thymine dinucleotide does not have a corresponding complementary sequence, it remains unbound to other sequences. Therefore, this TT portion is soft and can be arranged relatively freely. Therefore, this TT2 base plays a role of eliminating structural distortion that occurs when a planar structure is formed, and enables a wide planar structure.
  • T thymine
  • FIG. 45 is an enlarged view of the broken part with the planar structure peeled off. In some places, a square lattice structure can be seen. This appears to be a portion where the structure remains when the planar structure is broken. From this result, it can be said that DNA has a lattice-like planar structure.
  • nucleic acid is not limited to DNA, and a nucleic acid such as RNA or PNA may be used.
  • the nucleic acid structure and the nano nucleic acid structure according to the present embodiment may be formed by combining different nucleic acids such as RNA, DNA and PNA and hybridizing them.

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Abstract

L'invention porte sur un élément de construction d'acide nucléique disponible comme unité de construction dans la formation d'un produit de construction d'acide nanonucléique stable, qui a une résolution spatiale élevée, est riche en diversité et présente une contrainte réduite, et sur le produit de construction d'acide nanonucléique tel que décrit ci-dessus. L'invention porte sur un élément de construction d'acide nucléique caractérisé par le fait que la séquence de bases à l'extrémité libre d'un unique brin porté par une première molécule d'acide nucléique ayant une structure en double hélice est reliée par l'intermédiaire d'une liaison hydrogène à une séquence de bases située à une position définie dans la région non terminale d'un brin nucléotidique d'une seconde molécule d'acide nucléique ayant une structure en double hélice qui est une séquence de bases qui est non complémentaire de l'autre brin nucléotidique mais complémentaire de la séquence de bases à l'extrémité libre portée par la première molécule d'acide nucléique précédente.
PCT/JP2009/050720 2008-01-22 2009-01-20 Élément de construction d'acide nucléique, produit de construction d'acide nucléique utilisant celui-ci et procédé de fabrication du produit de construction d'acide nucléique WO2009093558A1 (fr)

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Cited By (6)

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WO2013022694A1 (fr) * 2011-08-05 2013-02-14 President And Fellows Of Harvard College Compositions et procédés associés à la nano- et micro-technologie d'acide nucléique
JP2014168831A (ja) * 2013-03-04 2014-09-18 Institute Of Physical & Chemical Research ポリヌクレオチドを用いたコイル及びその製造方法
US9975916B2 (en) 2012-11-06 2018-05-22 President And Fellows Of Harvard College Compositions and methods relating to complex nucleic acid nanostructures
US10099920B2 (en) 2014-05-22 2018-10-16 President And Fellows Of Harvard College Scalable nucleic acid-based nanofabrication
US10550145B2 (en) 2015-03-07 2020-02-04 President And Fellows Of Harvard College Single-stranded DNA nanostructures
US10604543B2 (en) 2012-07-24 2020-03-31 President And Fellows Of Harvard College Self-assembly of nucleic acid nanostructures

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JP2005263745A (ja) * 2004-03-19 2005-09-29 Research Institute Of Biomolecule Metrology Co Ltd 核酸化合物、核酸格子及び核酸多面体
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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013022694A1 (fr) * 2011-08-05 2013-02-14 President And Fellows Of Harvard College Compositions et procédés associés à la nano- et micro-technologie d'acide nucléique
CN103889998A (zh) * 2011-08-05 2014-06-25 哈佛学院院长等 涉及核酸纳米和微米技术的组合物和方法
US9796749B2 (en) 2011-08-05 2017-10-24 President And Fellows Of Harvard College Compositions and methods relating to nucleic acid nano- and micro-technology
US10604543B2 (en) 2012-07-24 2020-03-31 President And Fellows Of Harvard College Self-assembly of nucleic acid nanostructures
US9975916B2 (en) 2012-11-06 2018-05-22 President And Fellows Of Harvard College Compositions and methods relating to complex nucleic acid nanostructures
JP2014168831A (ja) * 2013-03-04 2014-09-18 Institute Of Physical & Chemical Research ポリヌクレオチドを用いたコイル及びその製造方法
US10099920B2 (en) 2014-05-22 2018-10-16 President And Fellows Of Harvard College Scalable nucleic acid-based nanofabrication
US10550145B2 (en) 2015-03-07 2020-02-04 President And Fellows Of Harvard College Single-stranded DNA nanostructures

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