55 results about "DNA origami" patented technology

The invention provides a molecular identity authentication system and method based on DNA origami framework layered assembly. The molecular identity authentication system comprises a disclosed skeleton chain and a plurality of shared staple chains, the shared staple chain comprises staple chains shared by three groups of single bodies and staple chains shared in pairs, and the staple chains are used as secret keys to be distributed to three participants so as to prepare the three groups of single bodies respectively, and then the three groups of single bodies are combined and spliced into a tripolymer with a dot matrix pattern, so that multi-user collaborative layered chain type assembly is realized. According to the molecular identity authentication system based on DNA origami framework layered assembly, the system combination complexity is improved to the information theory security level, so that the biological information security protection capability is improved, and brute force cracking is prevented.

The invention relates to polymer nanoparticle and DNA nanostructure delivery compositions for non-viral delivery, and methods therefor. More particularly, the invention relates to polymer nanoparticle delivery compositions, such as reversible addition-fragmentation chain transfer (RAFT) polymer compositions, and DNA nanostructure delivery compositions, such as DNA origami compositions, for the delivery of more than one payload, or for the delivery of a nucleic acid construct payload of 3 kB or more, and methods therefor.

The present disclosure relates to three-dimensional nucleic acid origami nanostructures that are designed to allow for self-assembly of the nanostructures into a larger structure (e.g., cylindrical, icosahedral, etc.) about the surface of a virus particle, and their use in treatment methods.

The invention relates to nucleic acid nanostructure delivery compositions for non-viral delivery, and methods therefor. More particularly, the invention relates to nucleic acid nanostructure delivery compositions, such as DNA origami compositions, for the delivery, for example, of small molecule therapeutics, and methods therefor.

Facet-based DNA polyhedral nanostructures with single strands of DNA for each polyhedron face. The DNA-based polyhedral nanostructures may be configured for targeted drug delivery and cell imaging for therapeutic, diagnostic and analytical diagnostic applications. The DNA polyhedral nanostructures adopt platonic icosahedral and dodecahedral configurations resembling the natural shapes of viral nucleocapsid proteins. The DNA polyhedral nanostructures address multiple technical challenges in the biomedical and biotechnological fields, including reducing the cost and complexity associated with conventional DNA origami systems, enhancing the sensitivity of diagnostic platforms, improving tracer delivery and signal clarity in PET and MRI, providing structural stability for nanostructure and payload integrity, and improving the resolution of Cryo-EM imaging of small molecules.

The invention provides a preparation method of a biological sample for diamond near-surface quantum sensing, and belongs to the field of quantum sensing detection. The method comprises the steps that a single-layer DNA origami structure is prepared, the single-layer DNA origami structure is provided with a pre-designed biological sample binding site, and the biological sample binding site is coupled with a biological sample through an interaction molecule pair; after the surface of the diamond is subjected to planarization pretreatment through plasma etching, nitrogen ions are injected to form an NV color center, and the diamond containing the NV color center is obtained; in a buffer solution environment containing cations, a solution containing the single-layer DNA origami structure and a to-be-detected biological sample solution are sequentially added to diamond for incubation, and the biological sample for diamond near-surface quantum sensing is obtained. The sample preparation method provides a reliable and efficient sample preparation basis for high-sensitivity and high-specificity single molecule / single particle biological sample detection based on diamond near-surface quantum sensing.

The present disclosure provides DNA origami nanoarrays, methods of synthesis thereof, and methods of use thereof.

The described method leverages nanosphere lithography (NSL) using nanoparticles having Young's modulus of at least 5 GPa, such as silica beads, to create high-density, periodic DNA origami nanoarrays on glass surfaces. In some aspects, by employing 1 μm silica beads, which have a higher Young's modulus compared to polystyrene beads, the sticky patch size (100 nm) is spaced out by 1 μm while maintaining DNA origami structures per spot. The resulting nanoarray consists of sticky patches with single DNA origami. This clean room-free fabrication method significantly reduces the cost per chip, while enabling precise positioning of target molecules at high throughput.

The present application belongs to the technical field of biology, and more particularly, the present application relates to a molecular computing method based on DNA origami technology and application thereof. The molecular computing method provided by the present application performs complex mathematical models by utilizing the addressing ability of DNA origami in positioning components and the programmability of DNA recognition, and the positioning of DNA components avoids the interference of diffusible chains, which is conducive to increasing the complexity of molecular reaction networks and opens up a new way for promoting molecular computing.

The application relates to a detection method based on a nano-addressable DNA origami platform combined with a CRISPR technology, in particular, a crRNA chain and a DNA fluorescent reporter molecule chain are hybridized at a preset spatial site through an address sequence, Cas12a is combined with the crRNA at a specific region, the activated Cas12a cuts a substrate, the fluorescent signal on the DNA origami changes, and thus the target nucleic acid is detected. The method of the application is suitable for various targets, and realizes simultaneous detection of multiple targets in a one-pot method.

This invention provides a DNA origami-based nanoscale ruler and its application. The nanoscale ruler includes a substrate structure, fluorescent indicator chains, and spacing indicator chains. The substrate structure is a three-layer rectangular structure constructed using DNA origami technology to maintain the basic configuration of the nanoscale ruler. Several fluorescent indicator chains are distributed on the first surface of the substrate structure according to a predetermined rule. These fluorescent indicator chains emit fluorescent signals through their fluorescent groups under specific excitation light. Two spacing indicator chains are disposed on the first surface of the substrate structure, forming a predetermined distance between them. These spacing indicator chains are used to target and bind to receptor proteins on the cell membrane via ligand proteins. One technical advantage of this invention is its rational design, which not only enables rapid and accurate determination of the presence of EGFR mutations in tissue samples but also effectively shortens the time required to determine the presence of EGFR mutations.

Provided herein are structures and methods for generating monoclonal clusters of a target oligonucleotide in a solution using a first nucleic acid supramolecular structure. In some cases, the target oligonucleotide is released from a second nucleic acid supramolecular structure. In some cases. the first and second nucleic acid supramolecular structure independently comprise DNA origami. In certain cases, the nucleic acid supramolecular structures may be coated in a hydrogel matrix. In other cases, the hydrogel matrix may be omitted. The monoclonal clusters created in solution using the disclosed structures and techniques may be immobilized on a substrate to facilitate subsequent processes performed on the monoclonal clusters.

The invention discloses a multivalent triangular DNA origami delivery system as well as a preparation method and application thereof, which can be used as a novel method for treating osteoarthritis, and is particularly suitable for patients with cartilage degeneration and joint inflammation caused by age, obesity, joint reuse, sport injury or genetic factors and the like. Specific siRNAs (small interfering RNAs) are delivered by the use of multivalent triangular DNA origami. According to the scheme, the expression of inflammation and degeneration related genes, such as Stat3, MMP3 and MMP13, in cartilage cells in joints can be specifically inhibited, so that the inflammatory response is relieved, cartilage decomposition is inhibited, and repair and regeneration of cartilage tissues are promoted. The invention provides a method for treating osteoarthritis, which has the advantages of strong targeting property, small side effect and obvious curative effect, is suitable for clinical treatment and basic medical research, and has wide application prospect.

The present invention relates to three-dimensional polynucleotide-based open shells for encapsulating viruses or viral particles, compositions comprising mixtures of such three-dimensional polynucleotide-based open shells, compositions comprising viruses or viral particles encapsulated by such three-dimensional polynucleotide-based open shells, and methods for encapsulating viruses, viral particles, or subviral particles by using such three-dimensional polynucleotide-based open shells.

This invention discloses a method for regulating the synergistic assembly of DNA origami. The method involves cutting a backbone chain to obtain several segmented backbone chains of different lengths, each segmented backbone chain having several enzyme cleavage sites. When the segmented backbone chains self-assemble with a third staple chain according to the base complementarity principle, the binding rate decreases, thereby regulating the synergistic assembly of DNA origami. The segmented backbone chains include a first staple chain, a second staple chain, and a single-stranded DNA strand of the backbone chain forming a partial double helix, which is then cleaved along the partial double helix by a cleaving enzyme to form several fragments of different lengths. This invention achieves effective regulation of the synergistic assembly of the backbone chain and staple chain in DNA origami technology by cutting the backbone chain. This method has wide applicability, requires no significant adjustment of the assembly buffer or temperature conditions, is not limited to the backbone chain structure, and has no impact on the final DNA origami structure.

Described herein is a novel nanostructured nucleic acid platform that uniquely integrates the advantages of disulfide moieties for enhanced cytoplasm uptake of DNA or RNA nanostructures ("DNA origami") that may further comprise a therapeutic agent and a targeting moiety. The targeting moiety may be an affinity, in particular a Her2 affinity. The disulfide moieties may be formed from sulfide modified oligonucleotides designed to target enhanced cytoplasm uptake.

The invention discloses a universal monodisperse DNA origami metal inorganic salt mineralization method and application thereof, the method comprises the following steps: (1) synthesizing a DNA origami structure and purifying by using a centrifugal filtration method to obtain a monodisperse DNA origami solution, and forming the monodisperse DNA origami solution through gradient annealing self-assembly of M13mp18 single-stranded DNA and a strile chain in a TAE buffer solution containing soluble metal salt; the nucleotide sequences of the striple chain are as shown in SEQ NO: 1-208; (2) adding soluble metal inorganic salt and a corresponding precipitant into the DNA origami solution, controlling the molar ratio of the basic group to the precipitant to be 1: 20-1: 80, reacting at 15-25 DEG C, and forming a metal inorganic salt mineralization coating layer on the surface of the DNA origami through electrostatic adsorption and precipitation growth, wherein the basic group refers to the total mole number of all nucleotide basic groups in the DNA origami structure; and (3) cleaning characterization. The product disclosed by the invention is excellent in monodispersity and high in colloidal stability; no organic coupling agent is needed, and the purity of the coating layer is high; the process is mild, simple to operate and easy to amplify.

Labelled DNA Origami for selective imaging of KRAS-mutant pancreatic cancer cells in a desmoplastic pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) are disclosed, as well as DNA Origami nanocomplexes for targeted delivery of a therapeutic payload to KRAS-mutant pancreatic cancer cells in a subject.

This invention relates to a catalyst, specifically a sub-10 nm catalyst and its self-assembly preparation method and application, comprising the following steps: pretreating DNA-modified Fe3O4 particles to remove free DNA strands; mixing scaffold DNA, short-chain DNA, and extended-chain DNA in a buffer solution and annealing to self-assemble into a DNA template; mixing the DNA-modified Fe3O4 particles and the DNA template in an incubation solution for co-incubation to obtain the catalyst. Compared with the prior art, this invention solves the problem of the difficulty in achieving precise quantity, accurate position, and consistent spacing of catalysts for CVD growth of CNTs with diameters less than 10 nm in the prior art. This method is based on the programmable characteristics of DNA origami, which allows for precise positioning of Fe3O4 nanoparticles, effectively controlling the spacing, arrangement, and concentration of the catalyst on the substrate, thereby achieving precise control of CVD growth of CNTs using this catalyst.

The invention relates to a DNA origami-based intracellular delivery platform for precisely targeting motor neurons, a DNA origami structure (BioDoori) comprises M13mp18 single-stranded DNA, biotin chains (biotin-DNA), fluorescent chains (fluorophore-DNA) and unmodified staple chains, each side of the DNA origami structure is loaded with 1-30 fluorescent chains and 1-10 biotin chains, and the biotin chains are loaded with 1-30 fluorescent groups and 1-10 fluorescent groups. The nucleotide sequence of the staple chain is as shown in SEQ ID NO: 1-208. According to the nano origami structure disclosed by the invention, accurate and efficient specific targeting aiming at motor neuron cells is realized, and lysosome escape efficacy of a DNA origami carrier is improved in a breakthrough manner.

The invention belongs to the technical field of biological medicines, and relates to a framework nucleic acid encoded aptamer-paclitaxel drug conjugate as well as a preparation method and application thereof. The six-spiral-beam DNA origami nanostructure has six tightly arranged spiral beams, can provide a stable platform for loading drugs and other molecules, can be used as an accurate addressing stent, can accurately control the spatial arrangement of aptamers and chemotherapeutic drugs, realizes efficient targeting, and has a good application prospect. Precise arrangement of paclitaxel can be effectively internalized by tumor cells, and the cytotoxic effect of paclitaxel can be played in the cells.

The present invention provides a use of SQB-DNA nanostructures, prepared using DNA origami technology, for inducing differentiation into nerve cells or nerve cell regeneration, or treating nerve damage or neurological diseases. The present invention is the first instance of achieving nerve recovery through precise ligand presentation using DNA origami nanostructures, and the widespread use of SQB as a therapeutic drug for various types of nerve damage and neurological diseases requiring nerve regeneration is expected due to the provision of the present invention.

The present disclosure is directed to compositions and methods that use the principles of DNA origami to package and archive data stored in multiple indexed DNA oligonucleotides. These structures allow for selective physical data access and retrieval from a molecular pool of DNA origami (DNAO) nanostructures comprising the data bearing oligonucleotides.

This invention proposes a tPA delivery system based on a tetrahedral DNA origami structure, its preparation method, and its applications, relating to the biomedical field. It includes a carrier composed of a tetrahedral DNA origami structure, a thrombus-targeting peptide, and short-chain DNA. The thrombus-targeting peptide and short-chain DNA are pre-coupled to form a peptide-short-chain complex, which is grafted onto the tetrahedral DNA origami structure. tPA and short-chain DNA are pre-coupled and loaded onto the edges of the tetrahedral DNA origami structure. Using the tetrahedral DNA origami structure as the core carrier, the vertices can be precisely modified with thrombus-targeting peptides to achieve targeting of the thrombus site. The tPA molecule is loaded onto the edges of the DNA origami structure via sulfo-SMCC linkage, and its release is controlled by introducing a thrombin-responsive DNA locking mechanism. This invention overcomes the limitations of current tPA thrombolytic therapy, enabling on-demand release of tPA during treatment, achieving local thrombolysis while reducing the risk of systemic bleeding.

The application discloses an antigen-specific T cell in-situ detection method and application, wherein pMHC monomers (peptide-MHC complexes) are nano-spatially organized on a DNA origami scaffold, the valence of pMHC is significantly improved, and stable combination with low-affinity T cells in a tissue slice is realized. Meanwhile, the precise addressing ability of the DNA origami and the design of a signal capture chain are utilized, and the amplification efficiency of a detection signal is greatly improved. In addition, a primer exchange reaction (PER reaction) is utilized to generate a single-stranded DNA product with repeated primer sequences (primer 1 and primer 2), a dendritic structure is formed on the DNA origami scaffold to combine multiple fluorescent groups, and antibody-independent high-fluorescence-intensity in-situ detection is realized, so that the experimental process is simplified and the detection cost is reduced.

Disclosed herein are DNA origami nanostmcture that can be functionalized for personalized and targeted drug delivery. The disclosed nanostructures enter cells through the endolysosomal pathway and circumvent drug resistance mechanisms in target cells. The disclosed nanostructures can be loaded small molecule drugs (e.g. anthracyclines, anti-metabolites) and nucleic acids (e.g. antisense oligonucleotides, siRNA, miRNA) with targeting and / or therapeutic antibodies against tumor-specific antigens (e.g. anti-CD33, anti-CD20) that can be modified to treat to a wide range of cancers and ultimately tailored to specific patients' needs for precision medicine.

The invention discloses a targeted protein degradation robot based on DNA origami as well as a construction method and application of the targeted protein degradation robot, and relates to the technical field of biological medicines. The targeted protein degradation robot comprises a DNA origami structure and a recognition module, the construction method of the DNA origami structure comprises the following steps: mixing M13 ssDNA with 60 stapled chains, carrying out annealing reaction to obtain DNA six-screw column origami, and carrying out incubation reaction on the DNA six-screw column origami and a P chain coupled with protease K to obtain origami coupled with inner layer protease K; performing incubation reaction on the origami coupled with the inner layer protease K, a T + S + A-ABD compound and an L + A-ABD compound to obtain an origami compound; and carrying out incubation reaction on the origami compound and human serum albumin (HSA) to obtain the DNA origami structure. The robot can achieve non-endogenous-dependence in-situ precise degradation of target protein, and a new strategy is provided for achieving treatment of diseases such as tumors through interference of the protein level.

The invention discloses an siRNA targeted delivery system based on DNA origami as well as a preparation method and application of the siRNA targeted delivery system. The siRNA targeted delivery system based on DNA origami comprises a DNA nano origami tube carrier, siRNA loaded in a tube cavity of the DNA nano origami tube carrier and targeted molecule-ssDNA conjugates modified at two ends of the DNA nano origami tube carrier, wherein the DNA nano origami tube carrier is mainly formed by self-assembling a bracket chain, a staple chain, a siRNA capture chain, an aptamer chain and a fastening chain. According to the siRNA targeted delivery system based on DNA origami provided by the invention, on one hand, long-acting protection of siRNA in serum and slow degradation and release in cells are realized by utilizing the tubular closed structure characteristic of the DNA nano origami tube carrier, the drug action time is prolonged, and the drug administration frequency is reduced; on the other hand, by modifying targeting molecules on the DNA nano origami tube carrier, the effects of inducing penetration of the blood brain barrier and targeted focus delivery can be achieved.

This invention discloses a single-degree-of-freedom DNA origami simulation mechanism and linkage mechanism with chiral transformation characteristics. The DNA origami simulation mechanism includes: a main folding unit comprising multiple main triangles arranged along the main folding direction, with adjacent main triangles forming a quadrilateral; and at least one secondary folding unit disposed on one side of the main folding unit, including a first folding area and a second folding area. The first folding area, the second folding area, and the main triangles are sequentially connected to form a folding center. The included angle of the first folding area at the folding center is β, and the vertex angle corresponding to the side of the main triangle shared with the second folding area is α. The included angle β is greater than the included angle α. This single-degree-of-freedom DNA origami simulation mechanism and linkage mechanism with chiral transformation characteristics overcomes the deficiencies in motion uncertainty, chiral switching, and torsional continuity.

The invention relates to a DNA origami biosensor capable of detecting at least two different target oligonucleotides at the same time, said biosensor comprising at least one DNA origami hinge and at least two detection sites, wherein each detection site comprises a signal emitting array, at least one lock and at least one movable section, wherein the movable sections of the detection sites are connected to each other or to a common DNA origami structure via the at least one hinge.