JPWO2019195633A5 - - Google Patents

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JPWO2019195633A5
JPWO2019195633A5 JP2020554139A JP2020554139A JPWO2019195633A5 JP WO2019195633 A5 JPWO2019195633 A5 JP WO2019195633A5 JP 2020554139 A JP2020554139 A JP 2020554139A JP 2020554139 A JP2020554139 A JP 2020554139A JP WO2019195633 A5 JPWO2019195633 A5 JP WO2019195633A5
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item
snap
support
solid support
binding
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JP2021520779A (en
JP7438966B2 (en
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Priority claimed from PCT/US2019/025909 external-priority patent/WO2019195633A1/en
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本発明の好ましい態様を本明細書において表示および記載したが、そのような態様は単に例として提供されることが当業者には明らかであろう。多数の変化、変更および置換が、本発明から逸脱することなく、当業者に今は想到されるだろう。本明細書に記載されている本発明の態様の様々な代替物が、本発明の実施において用いられ得ることが理解されるべきである。以下の特許請求の範囲は本発明の範囲を定義し、この特許請求の範囲の範囲内の方法および構造体ならびにそれらの等価物はそれによって保護されることが、意図される。
一態様において、本発明は以下を提供する。
(項目1)
タンパク質に共有結合している構造化核酸粒子(structured nucleic acid particle)(SNAP)を含む、組成物。
(項目2)
前記SNAPが固体支持体に結合している、項目1記載の組成物。
(項目3)
前記SNAPが固体支持体に共有結合している、項目2記載の組成物。
(項目4)
前記SNAPが固体支持体に非共有結合している、項目2記載の組成物。
(項目5)
生体分子に共有結合している核酸SNAPを含む、組成物。
(項目6)
前記SNAPが固体支持体に結合している、項目5記載の組成物。
(項目7)
前記SNAPが固体支持体に共有結合している、項目6記載の組成物。
(項目8)
前記SNAPが固体支持体に非共有結合している、項目6記載の組成物。
(項目9)
複数の構造化核酸粒子(SNAP)に結合している固体支持体を含む組成物であって、該複数のSNAPの各々が生体分子に結合している、組成物。
(項目10)
前記複数のSNAPがアレイ状に配置されている、項目9記載の組成物。
(項目11)
単一のタンパク質を固体支持体上の結合部位に結合させる方法であって、
該結合部位が該タンパク質より大きく;
該方法が、
該タンパク質を構造化核酸粒子(SNAP)に共有結合させる工程であって、該SNAPの直径が少なくとも該結合部位の直径と同じ大きさである、工程;および
該核酸SNAPを該結合部位に結合させる工程
を含む、方法。
(項目12)
各結合部位が単一のタンパク質に結合するように、複数の前記タンパク質の各々が前記固体支持体上の結合部位に結合する、項目11記載の方法。
(項目13)
固体支持体に結合している複数の生体分子を含む生体分子アレイであって、該複数の生体分子の各生体分子がリンカーに共有結合しており、該リンカーが該固体支持体に結合しており、かつ各リンカーが該複数の生体分子のうちの一つの生体分子のみに結合しており、各リンカーが少なくとも50nmの直径を有する、生体分子アレイ。
(項目14)
複数のタンパク質から空間的に分離されているタンパク質のアレイを製造する方法であって、該複数のタンパク質の各タンパク質を、構造化核酸粒子(SNAP)を構成する核酸分子の末端に共有結合させる工程、該SNAPを固体支持体に結合させる工程を含み、それによって空間的に分離されているタンパク質のアレイを製造する、方法。
(項目15)
タンパク質、構造化核酸粒子(SNAP)、および固体支持体を含む組成物であって、該タンパク質が該SNAPに共有結合しており、かつ該タンパク質が該固体支持体に接触していない、組成物。
(項目16)
空間的に分離されている生物学的または化学的実体のアレイを製造する方法であって、
結合部位を有する固体支持体を得る工程、
複数の生物学的または化学的実体を含むサンプルを得る工程、
各々が官能基を有するシードを得る工程、
該複数の生物学的または化学的実体の各生物学的または化学的実体を、該官能基を介して単一のシードに共有結合させる工程、
結合した各シードを所望のサイズの構造化核酸粒子(SNAP)へと成長させる工程、
該SNAPを該アレイの結合部位に結合させる工程
を含み、
それによって、空間的に分離されている生物学的または化学的実体のアレイを製造する、方法。
(項目17)
前記固体支持体がガラス支持体である、項目16記載の方法。
(項目18)
前記固体支持体がシリカ支持体である、項目16記載の方法。
(項目19)
前記固体支持体がプラスチック支持体である、項目16記載の方法。
(項目20)
前記固体支持体がシリコン支持体である、項目16記載の方法。
(項目21)
前記固体支持体が金支持体である、項目16記載の方法。
(項目22)
前記固体支持体が金属支持体である、項目16記載の方法。
(項目23)
前記固体支持体がクロム支持体である、項目16記載の方法。
(項目24)
前記固体支持体がチタン支持体である、項目16記載の方法。
(項目25)
前記固体支持体が酸化チタン支持体である、項目16記載の方法。
(項目26)
前記固体支持体がスズ支持体である、項目16記載の方法。
(項目27)
前記固体支持体が酸化スズ支持体である、項目16記載の方法。
(項目28)
前記固体支持体が光学的に不透明である、項目16記載の方法。
(項目29)
前記固体支持体が光学的に透明である、項目16記載の方法。
(項目30)
前記固体支持体が、正電荷を有するように修飾されている、項目16記載の方法。
(項目31)
前記固体支持体が、負電荷を有するように修飾されている、項目16記載の方法。
(項目32)
前記固体支持体が、前記SNAPに結合し得る官能基を有するように修飾されている、項目16記載の方法。
(項目33)
前記固体支持体が、周囲の表面とは異なるように修飾されている結合部位を含む、項目16記載の方法。
(項目34)
前記固体支持体が結合部位のアレイを含む、項目27記載の方法。
(項目35)
各結合部位が、他の結合部位の各々から少なくとも70nm離れている、項目34記載の方
法。
(項目36)
各結合部位が、他の結合部位の各々から少なくとも25nm離れている、項目34記載の方法。
(項目37)
任意の2つの結合部位の端部間の距離が、使用される前記SNAPの半径よりも大きい、項目34記載の方法。
(項目38)
任意の2つの結合部位の端部間の距離が、使用される前記SNAPの直径よりも大きい、項目34記載の方法。
(項目39)
前記分子がタンパク質である、項目16記載の方法。
(項目40)
前記シードがオリゴヌクレオチドである、項目16記載の方法。
(項目41)
前記オリゴヌクレオチドの3'末端が官能基で修飾されている、項目40記載の方法。
(項目42)
前記オリゴヌクレオチドの5'末端が官能基で修飾されている、項目40記載の方法。
(項目43)
前記官能基が、アミン、チオール、カルボン酸、三重結合、二重結合、エポキシド、アルキン、アルケン、シクロアルキン、アジド、シクロオクチン、シクロアルキン、ノルボルネン、テトラジン、シクロオクタン、エポキシド、およびヒドロキシルからなる群より選択される、項目41または42のいずれか一項記載の方法。
(項目44)
前記オリゴヌクレオチドが、光切断可能な結合を含むように修飾されている、項目40記載の方法。
(項目45)
前記SNAPがローリングサークル増幅によって形成される、項目16記載の方法。
(項目46)
前記SNAPがデンドリマーである、項目16記載の方法。
(項目47)
前記デンドリマーが正に帯電している、項目46記載の方法。
(項目48)
前記アレイ上の結合部位が負に帯電している、項目47記載の方法。
(項目49)
前記デンドリマーが負に帯電している、項目46記載の方法。
(項目50)
前記アレイ上の結合部位が正に帯電している、項目49記載の方法。
(項目51)
前記SNAPがおよそ100nmの直径を有する、項目50記載の方法。
(項目52)
前記SNAPがおよそ300nmの直径を有する、項目45記載の方法。
(項目53)
前記SNAPが約10nm~500μmの直径を有する、項目45記載の方法。
(項目54)
前記SNAPが約10nm~50μmの直径を有する、項目45記載の方法。
(項目55)
前記SNAPが約10nm~5μmの直径を有する、項目45記載の方法。
(項目56)
前記SNAPが約100nm~500nmの直径を有する、項目45記載の方法。
(項目57)
前記SNAPが、静電相互作用を通じて前記固体支持体に付着する、項目45記載の方法。
(項目58)
分子の空間的分離を達成する方法であって、
複数の分子を得る工程、
各々が官能基を有するシードを得る工程、
該複数の分子の各々を、該官能基を介して単一のシードに共有結合させる工程、
結合した各シードを、所望のサイズの構造化核酸粒子(SNAP)へと成長させる工程、
該SNAPを固体支持体に結合させる工程
を含み、
それによって単一分子の空間的分離を達成する、方法。
(項目59)
単一分子のアレイであって、各単一分子が所望のサイズの構造化核酸粒子(SNAP)に結合しており、該SNAPが該結合部位を介してアレイに結合している、単一分子のアレイ。
(項目60)
単一分子のアレイを製造するためのキットであって、
結合部位を有するアレイ、
各シードが単一の結合部位を有する、シード、および
該シードを構造化核酸粒子(SNAP)へと成長させるための試薬
を含む、キット。
(項目61)
固体支持体;および
該固体支持体に直接結合しているポリマーベースの分子であって、該ポリマーベースの分子が、実質的に該固体支持体の反対側に配置されているタンパク質部分を含み、かつ、該タンパク質部分が親和性試薬にアクセス可能である、ポリマーベースの分子
を含む、組成物。
(項目62)
アレイ上で生物学的または化学的実体を隔離する方法であって、
複数の構造化核酸粒子(SNAP)を作製する工程;
単一の生物学的または化学的実体を該複数のSNAPの各々にカップリングさせる工程;
該複数のSNAPをアレイに結合させる工程であって、該生物学的または化学的実体が実質的に該アレイの反対側にある、工程
を含み、
それによって、該複数のSNAPの各々の各生物学的または化学的実体を、該複数のSNAPの各SNAPのサイズに基づく距離だけ隔離する、方法。
(項目63)
分子を分離する方法であって、各分子をより大きな荷電分子に変換する工程を含む、方法。
(項目64)
各分子をより大きな荷電分子に変換する工程が、所望のサイズへと成長することができるバイオポリマーに該分子をコンジュゲートさせることを含む、項目63記載の方法。
(項目65)
各分子をより大きな荷電分子に変換する工程が、各分子を10倍大きい分子に変換することを含む、項目63記載の方法。
(項目66)
各分子をより大きな荷電分子に変換する工程が、各分子をより大きな荷電分子にコンジュゲートさせることを含む、項目63記載の方法。
(項目67)
空間的に分離されている生物学的または化学的実体のアレイを製造する方法であって、
結合部位を有する固体支持体を得る工程、
複数の生物学的または化学的実体を含むサンプルを得る工程、
各々が官能基を有する構造化核酸粒子(SNAP)を得る工程、
該複数の生物学的または化学的実体の各生物学的または化学的実体を単一のSNAPに共有結合させる工程、
該SNAPを該アレイの該結合部位に結合させる工程、
を含み、
それによって、空間的に分離されている生物学的または化学的実体のアレイを製造する、方法。
(項目68)
前記SNAPがローリングサークル増幅産物である、前記項目のいずれか一項記載の組成物。
(項目69)
前記SNAPがプラスミドである、前記項目のいずれか一項記載の組成物。
(項目70)
前記SNAPがDNA折り紙分子である、前記項目のいずれか一項記載の組成物。
(項目71)
前記SNAPが核酸クラスターである、前記項目のいずれか一項記載の方法。
(項目72)
前記SNAPがローリングサークル増幅産物である、前記項目のいずれか一項記載の方法。
(項目73)
前記SNAPがプラスミドである、前記項目のいずれか一項記載の方法。
(項目74)
前記SNAPがDNA折り紙分子である、前記項目のいずれか一項記載の方法。
(項目75)
前記SNAPが核酸クラスターである、前記項目のいずれか一項記載の方法。
(項目76)
前記SNAPがローリングサークル増幅産物である、前記項目のいずれか一項記載のキット。
(項目77)
前記SNAPがプラスミドである、前記項目のいずれか一項記載のキット。
(項目78)
前記SNAPがDNA折り紙分子である、前記項目のいずれか一項記載のキット。
(項目79)
前記SNAPが核酸クラスターである、前記項目のいずれか一項記載のキット。


Although preferred embodiments of the invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided merely by way of example. Numerous changes, changes and substitutions will now be conceived by those of skill in the art without departing from the present invention. It should be understood that various alternatives of aspects of the invention described herein can be used in the practice of the invention. The following claims define the scope of the invention, and it is intended that the methods and structures within the scope of this claim and their equivalents are protected by it.
In one aspect, the invention provides:
(Item 1)
A composition comprising structured nucleic acid particles (SNAPs) that are covalently attached to a protein.
(Item 2)
The composition according to item 1, wherein the SNAP is bound to a solid support.
(Item 3)
Item 2. The composition according to item 2, wherein the SNAP is covalently bonded to a solid support.
(Item 4)
The composition according to item 2, wherein the SNAP is non-covalently bonded to a solid support.
(Item 5)
A composition comprising the nucleic acid SNAP covalently attached to a biomolecule.
(Item 6)
5. The composition of item 5, wherein the SNAP is attached to a solid support.
(Item 7)
Item 6. The composition according to item 6, wherein the SNAP is covalently bonded to a solid support.
(Item 8)
6. The composition of item 6, wherein the SNAP is non-covalently attached to a solid support.
(Item 9)
A composition comprising a solid support attached to a plurality of structured nucleic acid particles (SNAPs), wherein each of the plurality of SNAPs is bound to a biomolecule.
(Item 10)
Item 9. The composition according to item 9, wherein the plurality of SNAPs are arranged in an array.
(Item 11)
A method of binding a single protein to a binding site on a solid support.
The binding site is larger than the protein;
The method is
A step of covalently binding the protein to a structured nucleic acid particle (SNAP), wherein the diameter of the SNAP is at least as large as the diameter of the binding site;
Step of binding the nucleic acid SNAP to the binding site
Including, how.
(Item 12)
11. The method of item 11, wherein each of the plurality of proteins binds to a binding site on the solid support such that each binding site binds to a single protein.
(Item 13)
A biomolecule array containing a plurality of biomolecules attached to a solid support, wherein each biomolecule of the plurality of biomolecules is covalently attached to a linker, and the linker is attached to the solid support. A biomolecule array in which each linker is attached to only one of the plurality of biomolecules, and each linker has a diameter of at least 50 nm.
(Item 14)
A method for producing an array of proteins that are spatially separated from a plurality of proteins, in which each protein of the plurality of proteins is covalently bonded to the terminal of a nucleic acid molecule constituting a structured nucleic acid particle (SNAP). , A method comprising the step of binding the SNAP to a solid support, thereby producing an array of spatially separated proteins.
(Item 15)
A composition comprising a protein, structured nucleic acid particles (SNAP), and a solid support, wherein the protein is covalently attached to the SNAP and the protein is not in contact with the solid support. ..
(Item 16)
A method of producing an array of spatially separated biological or chemical entities.
The process of obtaining a solid support with a binding site,
The process of obtaining a sample containing multiple biological or chemical entities,
Steps to obtain seeds, each with a functional group,
A step of covalently attaching each biological or chemical entity of the plurality of biological or chemical entities to a single seed via the functional group.
The process of growing each bound seed into structured nucleic acid particles (SNAP) of the desired size,
Step of binding the SNAP to the binding site of the array
Including
A method of producing an array of spatially separated biological or chemical entities.
(Item 17)
Item 16. The method according to item 16, wherein the solid support is a glass support.
(Item 18)
Item 16. The method according to item 16, wherein the solid support is a silica support.
(Item 19)
Item 16. The method according to item 16, wherein the solid support is a plastic support.
(Item 20)
Item 16. The method according to item 16, wherein the solid support is a silicon support.
(Item 21)
Item 16. The method according to item 16, wherein the solid support is a gold support.
(Item 22)
Item 16. The method according to item 16, wherein the solid support is a metal support.
(Item 23)
16. The method of item 16, wherein the solid support is a chrome support.
(Item 24)
Item 16. The method according to item 16, wherein the solid support is a titanium support.
(Item 25)
Item 16. The method according to item 16, wherein the solid support is a titanium oxide support.
(Item 26)
Item 16. The method according to item 16, wherein the solid support is a tin support.
(Item 27)
Item 16. The method according to item 16, wherein the solid support is a tin oxide support.
(Item 28)
16. The method of item 16, wherein the solid support is optically opaque.
(Item 29)
Item 16. The method of item 16, wherein the solid support is optically transparent.
(Item 30)
16. The method of item 16, wherein the solid support is modified to have a positive charge.
(Item 31)
16. The method of item 16, wherein the solid support is modified to have a negative charge.
(Item 32)
16. The method of item 16, wherein the solid support is modified to have a functional group capable of binding to the SNAP.
(Item 33)
16. The method of item 16, wherein the solid support comprises a binding site in which the solid support is modified to be different from the surrounding surface.
(Item 34)
27. The method of item 27, wherein the solid support comprises an array of binding sites.
(Item 35)
Item 34, wherein each binding site is at least 70 nm away from each of the other binding sites.
Law.
(Item 36)
34. The method of item 34, wherein each binding site is at least 25 nm away from each of the other binding sites.
(Item 37)
34. The method of item 34, wherein the distance between the ends of any two binding sites is greater than the radius of said SNAP used.
(Item 38)
34. The method of item 34, wherein the distance between the ends of any two binding sites is greater than the diameter of said SNAP used.
(Item 39)
16. The method of item 16, wherein the molecule is a protein.
(Item 40)
16. The method of item 16, wherein the seed is an oligonucleotide.
(Item 41)
40. The method of item 40, wherein the 3'end of the oligonucleotide is modified with a functional group.
(Item 42)
40. The method of item 40, wherein the 5'end of the oligonucleotide is modified with a functional group.
(Item 43)
The group in which the functional group consists of amine, thiol, carboxylic acid, triple bond, double bond, epoxide, alkyne, alkyne, cycloalkyne, azide, cyclooctyne, cycloalkyne, norbornen, tetradine, cyclooctane, epoxide, and hydroxyl. The method according to any one of items 41 or 42, which is selected from.
(Item 44)
40. The method of item 40, wherein the oligonucleotide is modified to contain a photocleavable bond.
(Item 45)
16. The method of item 16, wherein the SNAP is formed by rolling circle amplification.
(Item 46)
Item 16. The method according to item 16, wherein the SNAP is a dendrimer.
(Item 47)
46. The method of item 46, wherein the dendrimer is positively charged.
(Item 48)
47. The method of item 47, wherein the binding site on the array is negatively charged.
(Item 49)
46. The method of item 46, wherein the dendrimer is negatively charged.
(Item 50)
49. The method of item 49, wherein the binding site on the array is positively charged.
(Item 51)
50. The method of item 50, wherein the SNAP has a diameter of approximately 100 nm.
(Item 52)
45. The method of item 45, wherein the SNAP has a diameter of approximately 300 nm.
(Item 53)
45. The method of item 45, wherein the SNAP has a diameter of about 10 nm to 500 μm.
(Item 54)
45. The method of item 45, wherein the SNAP has a diameter of about 10 nm to 50 μm.
(Item 55)
45. The method of item 45, wherein the SNAP has a diameter of about 10 nm to 5 μm.
(Item 56)
45. The method of item 45, wherein the SNAP has a diameter of about 100 nm to 500 nm.
(Item 57)
45. The method of item 45, wherein the SNAP adheres to the solid support through electrostatic interaction.
(Item 58)
A way to achieve spatial separation of molecules,
The process of obtaining multiple molecules,
Steps to obtain seeds, each with a functional group,
A step of covalently attaching each of the plurality of molecules to a single seed via the functional group.
The step of growing each bound seed into structured nucleic acid particles (SNAP) of the desired size,
Step of binding the SNAP to a solid support
Including
A method that thereby achieves spatial separation of a single molecule.
(Item 59)
A single molecule array in which each single molecule is attached to a structured nucleic acid particle (SNAP) of the desired size, and the SNAP is attached to the array via the binding site. Array of.
(Item 60)
A kit for manufacturing single molecule arrays,
Arrays with binding sites,
Each seed has a single binding site, the seed, and
Reagents for growing the seed into structured nucleic acid particles (SNAP)
Including, kit.
(Item 61)
Solid support; and
A polymer-based molecule that is directly attached to the solid support, wherein the polymer-based molecule comprises a protein moiety that is located substantially opposite the solid support and the protein moiety. Are accessible to affinity reagents, polymer-based molecules
A composition comprising.
(Item 62)
A method of isolating biological or chemical entities on an array,
The process of producing multiple structured nucleic acid particles (SNAP);
The process of coupling a single biological or chemical entity to each of the multiple SNAPs;
A step of binding the plurality of SNAPs to an array, wherein the biological or chemical entity is substantially on the opposite side of the array.
Including
A method thereby isolating each biological or chemical entity of each of the plurality of SNAPs by a distance based on the size of each SNAP of the plurality of SNAPs.
(Item 63)
A method of separating molecules, comprising the step of converting each molecule into a larger charged molecule.
(Item 64)
63. The method of item 63, wherein the step of converting each molecule to a larger charged molecule comprises conjugating the molecule to a biopolymer capable of growing to a desired size.
(Item 65)
63. The method of item 63, wherein the step of converting each molecule to a larger charged molecule comprises converting each molecule into a 10-fold larger molecule.
(Item 66)
63. The method of item 63, wherein the step of converting each molecule to a larger charged molecule comprises conjugating each molecule to a larger charged molecule.
(Item 67)
A method of producing an array of spatially separated biological or chemical entities.
The process of obtaining a solid support with a binding site,
The process of obtaining a sample containing multiple biological or chemical entities,
Steps to obtain structured nucleic acid particles (SNAP), each with a functional group,
The step of covalently binding each biological or chemical entity of the plurality of biological or chemical entities to a single SNAP.
The step of binding the SNAP to the binding site of the array,
Including
A method of producing an array of spatially separated biological or chemical entities.
(Item 68)
The composition according to any one of the above items, wherein the SNAP is a rolling circle amplification product.
(Item 69)
The composition according to any one of the above items, wherein the SNAP is a plasmid.
(Item 70)
The composition according to any one of the above items, wherein the SNAP is a DNA origami molecule.
(Item 71)
The method according to any one of the above items, wherein the SNAP is a nucleic acid cluster.
(Item 72)
The method according to any one of the above items, wherein the SNAP is a rolling circle amplification product.
(Item 73)
The method according to any one of the above items, wherein the SNAP is a plasmid.
(Item 74)
The method according to any one of the above items, wherein the SNAP is a DNA origami molecule.
(Item 75)
The method according to any one of the above items, wherein the SNAP is a nucleic acid cluster.
(Item 76)
The kit according to any one of the above items, wherein the SNAP is a rolling circle amplification product.
(Item 77)
The kit according to any one of the above items, wherein the SNAP is a plasmid.
(Item 78)
The kit according to any one of the above items, wherein the SNAP is a DNA origami molecule.
(Item 79)
The kit according to any one of the above items, wherein the SNAP is a nucleic acid cluster.


Claims (15)

単一のタンパク質を固体支持体上の結合部位に結合させる方法であって、
該方法が、
単一のタンパク質を構造化核酸粒子(SNAP)に共有結合させる工程であって、該SNAPの直径が少なくとも該結合部位の直径と同じ大きさである、工程;および
該結合部位が該単一のタンパク質に結合するように、SNAPを該結合部位に結合させる工程
を含む、方法。
A method of binding a single protein to a binding site on a solid support.
The method is
A step of covalently binding the single protein to a structured nucleic acid particle (SNAP), wherein the diameter of the SNAP is at least as large as the diameter of the binding site;
A method comprising binding the SNAP to the binding site such that the binding site binds to the single protein .
前記固体支持体がガラス支持体、シリカ支持体、プラスチック支持体、シリコン支持体、金支持体、金属支持体、クロム支持体、チタン支持体、酸化チタン支持体、スズ支持体、または酸化スズ支持体である、請求項記載の方法。 The solid support is a glass support , a silica support, a plastic support, a silicon support, a gold support, a metal support, a chromium support, a titanium support, a titanium oxide support, a tin support, or a tin support. The method according to claim 1 , which is a body . 前記固体支持体が光学的に不透明または透明である、請求項記載の方法。 2. The method of claim 2 , wherein the solid support is optically opaque or transparent . 前記固体支持体が、正電荷または負電荷を有するように修飾されている、請求項記載の方法。 The method of claim 2 , wherein the solid support is modified to have a positive or negative charge . 前記固体支持体が、前記SNAPを前記結合部位に結合させる前に不動態化されている、請求項記載の方法。 The method of claim 2 , wherein the solid support is passivated prior to binding the SNAP to the binding site . 前記固体支持体が結合部位のアレイを含む、請求項記載の方法。 The method of claim 1 , wherein the solid support comprises an array of binding sites. 各結合部位が、他の結合部位の各々から少なくとも70nmまたは少なくとも25nm離れている、請求項記載の方法。 The method of claim 6 , wherein each binding site is at least 70 nm or at least 25 nm away from each of the other binding sites. 任意の2つの結合部位の端部間の距離が、記SNAPの半径または直径よりも大きい、請求項記載の方法。 6. The method of claim 6 , wherein the distance between the ends of any two binding sites is greater than the radius or diameter of the SNAP. 前記SNAPが、光切断可能な結合を含むように修飾されている、請求項記載の方法。 The method of claim 1 , wherein the SNAP is modified to include a photocleavable bond. 前記SNAPがローリングサークル増幅によって形成される、請求項記載の方法。 The method of claim 1 , wherein the SNAP is formed by rolling circle amplification. 前記SNAPが核酸折り紙を含み、該核酸折り紙がデオキシリボ核酸(DNA)またはリボデオキシリボ核酸(RNA)を含んでもよい、請求項記載の方法。 The method according to claim 1 , wherein the SNAP may contain nucleic acid origami, which may contain deoxyribonucleic acid (DNA) or ribodeoxyribonucleic acid (RNA) . 前記SNAPがおよそ100nmまたはおよそ300nmの直径を有する、請求項記載の方法。 The method of claim 1 , wherein the SNAP has a diameter of about 100 nm or about 300 nm . 前記SNAPが約10nm~500μmの直径を有する、請求項記載の方法。 The method of claim 1 , wherein the SNAP has a diameter of about 10 nm to 500 μm. 前記SNAPが、静電相互作用を通じて前記固体支持体に付着する、請求項記載の方法。 The method of claim 1 , wherein the SNAP adheres to the solid support through electrostatic interaction. 前記SNAPが、リンカーにより前記単一のタンパク質に共有結合されており、該リンカーがPEG、DNA、短いカルボキシル、炭素鎖、ペプトイド、スペーサー、グリセル(glycer)から選択されるものを含んでもよい、請求項1に記載の方法。The SNAP is covalently attached to the single protein by a linker, and the linker may include one selected from PEG, DNA, short carboxyl, carbon chains, peptoids, spacers, glycer. Item 1. The method according to Item 1.
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