35 results about "Spherical nucleic acid" patented technology

The disclosure generally provides biradial spherical nucleic acids (SNAs), compositions comprising a biradial SNA or a plurality thereof, and methods of making and using the biradial SNAs. In some aspects, the disclosure provides a biradial spherical nucleic acid (SNA) comprising: (a) a liposomal core comprising an outer leaflet and an inner leaflet; and (b) a population of oligonucleotides attached to the liposomal core, the population of oligonucleotides comprising: (i) a first plurality of oligonucleotides attached to the outer leaflet of the liposomal core and radiating outward from the liposomal core; and (ii) a second plurality of oligonucleotides attached to the inner leaflet of the liposomal core and radiating inward into the liposomal core, wherein one or more or all of the second plurality of oligonucleotides is a nuclease resistant oligonucleotide. In some embodiments, the first plurality of oligonucleotides and the second plurality of oligonucleotides are different.

The present invention discloses a method for imaging primary neuronal cells using a dual-modal bio-orthogonal spherical nucleic acid probe, comprising the following steps: 1) designing a DNA sequence modified with a click reaction functional group, a fluorescent group, and labeled with a thiol or polyadenine; 2) preparing a BO-SNAs probe from the DNA sequence and a probe core material; 3) extracting and culturing primary neuronal cells; 4) co-incubating the cells with a click reaction functional group modification reagent; 5) labeling the cells with the BO-SNAs probe using a click reaction; and 6) imaging the primary neuronal cells. This method is the first to use bio-orthogonal click reaction-based BO-SNAs probes to label neuronal cells for synchrotron X-ray imaging, providing new ideas for the design of synchrotron X-ray imaging probes and a new tool for synchrotron X-ray-based brain imaging.

The present disclosure is directed to spherical nucleic acids (SNAs) comprising a nanoparticle core and an oligonucleotide shell attached to the external surface of the nanoparticle core, wherein the oligonucleotide shell comprises a mixture of class A CpG oligonucleotides and class B CpG oligonucleotides. The disclosure also provides methods of using the SNAs for, e.g., regulation of an immune response and gene regulation.

Disclosed herein are spherical nucleic acids (SNAs) comprising oligonucleotides comprising one or more modified oligonucleotides, and methods of use thereof. Also disclosed are methods of synthesizing modified oligonucleotides for use in therapeutics, including deoxynucleic guanidine (DNG)-modified oligonucleotides.

Spherical nucleic acids (SNAs) are an attractive platform for therapeutic delivery due to their chemically tunable structures, biocompatibility, and ability to rapidly enter cells without transfection reagents. The present disclosure provides SNAs and strategies for delivering gene editing proteins into cells. The delivered gene editing proteins remain enzymatically active and rapidly enter mammalian cells.

The disclosure is generally directed to spherical nucleic acids (SNAs), nanostructures with a core surrounded by a radial presentation of oligonucleotides, that can activate a cytoplasmic DNA sensor including but not limited to cyclic GMP-AMP synthase (cGAS). In some embodiments, the SNAs also inactivate a transcription factor including but not limited to signal transducer and activator of transcription 3 (STATS). Methods of making and using the SNAs are also provided herein. In some aspects, the present disclosure provides a spherical nucleic acid (SNA) comprising (a) a nanoparticle core; and (b) a shell of oligonucleotides attached to the external surface of the nanoparticle core, the shell of oligonucleotides comprising a double-stranded or single-stranded stem loop DNA oligonucleotide that activates cyclic GMP-AMP synthase (cGAS) and is at least 15 base pairs in length.

The present invention provides a dengue polypeptide vaccine based on spherical nucleic acid carriers, its preparation method and application, belonging to the technical field of vaccine adjuvants. The present invention provides a polypeptide TBB, whose amino acid sequence is shown in SEQ ID NO.1. The present invention constructs a dengue polypeptide vaccine based on spherical nucleic acid carriers by using the polypeptide TBB. This dengue polypeptide vaccine can effectively present antigens to BMDCs, stimulate the maturation and activation of BMDCs, effectively solve the problem of poor immunogenicity of polypeptide vaccines, and at the same time exhibit good biosafety.

It is possible to synthesize liposomes known as "small unilamellar vesicles" (SUVs) in the 20–50 nm size range, but they face obstacles such as instability and aggregation leading to fusion between particles. This limits their use as a therapeutic delivery agent. Increasing the negative surface charge of SUVs by binding anionic entities such as DNA / RNA enhances the colloidal stability of these vesicles. Additionally, the dense spherical arrangement and radial orientation of nucleic acids exhibit unique biological and chemical properties, unlike their linear counterparts. These liposomal particles are non-toxic and, although anionic, can efficiently enter cells without the aid of cationic transfection agents in a non-immunogenic manner.These exceptional properties allow their use as delivery agents for gene regulation in different therapies and offer an alternative platform to metal-core spherical nucleic acids.

Aspects of the invention relate to immunostimulatory spherical nucleic acids (IS-SNA) for the treatment of a disorder, such as cancer. The IS-SNA may be administered together with a checkpoint inhibitor.

The invention discloses a triblock single-stranded nucleic acid, a spherical nucleic acid probe, preparation and application of the spherical nucleic acid probe and a virus detection kit. The three-block single-stranded nucleic acid sequentially comprises an assembly structural domain, a hybridization structural domain and a report structural domain, the three-block single-stranded nucleic acid is adsorbed on the surface of the nano particle through the assembly structural domain, and the three-block single-stranded nucleic acid and the hybridization DNA form a complementary double-stranded structure to obtain the spherical nucleic acid probe. The method for detecting the virus by using the spherical nucleic acid probe comprises the following steps: designing and synthesizing crRNA by using a target sequence; carrying out incubation on the crRNA and CRISPR nuclease to construct a binary complex; mixing the spherical nucleic acid probe and to-be-detected viral nucleic acid with the binary complex solution, incubating, and detecting the change of fluorescence intensity. The virus detection kit comprises a spherical nucleic acid probe and a binary complex. The spherical nucleic acid probe based on the three-block single-stranded nucleic acid extension configuration can effectively improve the virus nucleic acid detection efficiency. The virus detection method has high specificity and capability of rapidly detecting virus nucleic acid.

The invention belongs to the technical field of biomimetic materials, and particularly relates to a gold nanomaterial positively coated with a cell membrane as well as a preparation method and application of the gold nanomaterial. The cell membrane forward coated gold nanomaterial comprises a gold nanomaterial and a cell membrane layer coated on the surface of the gold nanomaterial, the inner membrane of the cell membrane layer faces the gold nano material, and the cell membrane layer is connected with the gold nano material through biotin-streptavidin non-covalent bonding. Selectively modifying biotin in the cell endomembrane by using the membrane fusion spherical nucleic acid, and extracting to obtain an endomembrane biotinylated cell membrane; the preparation method comprises the following steps: co-incubating a streptavidin functionalized gold nanomaterial and a cell membrane, and realizing forward ordered coating of the cell membrane through biotin-streptavidin specific binding. The material prepared by the invention has the characteristics of simple preparation method, mild conditions, ordered cell membrane coating and high coating rate. The cell membrane forward coated nano material can be used for targeted delivery of drugs to realize precise diagnosis and treatment of cancers.

The present invention provides a spherical nucleic acid based on a double-block DNA probe, and a preparation method and application thereof. The spherical nucleic acid uses gold nanoparticles as a carrier, and a double-block DNA probe is modified on its surface. The double-block DNA probe consists of AP, polyA20-TP and FP modified with a fluorescent group. PolyA20 is modified on the surface of the gold nanoparticles, and the spherical nucleic acid is driven to run by the fuel chain FS to achieve room temperature enzyme-free target cyclic amplification. The nucleic acid detection method provided by the present invention utilizes the target and the FP chain with a fluorescent group to be replaced by the fuel chain at the same time. The fluorescent group is away from the surface of the gold nanoparticle, emits light in the solution, and the fluorescence signal is significantly enhanced. As the target concentration increases, the intensity of the fluorescent signal also increases. In a 1×PBS buffer system, the detection limit of this method is 228.7pM. In a complex system of 100% FBS, the detection limit of this method is 6.61nM.

The invention relates to sound-sensitive supramolecular spherical nucleic acid as well as a preparation method and application thereof. The sound-sensitive supramolecular spherical nucleic acid is mainly applied to immunotherapy of oral leukoplakia. The supramolecular spherical nucleic acid is formed by a dendrimer core modified by a sound-sensitive agent and beta-CD and a nucleic acid shell modified by ferrocene through a subject-object recognition effect. Compared with a traditional treatment method, the spherical nucleic acid prepared by the invention not only has more excellent sonodynamic effect and immune activation ability, but also can realize transdermal drug delivery of oral cavity diseased tissues. The transdermal administration route can not only improve the drug enrichment effect of the focus part and realize precise treatment, but also reduce the drug metabolism burden and potential toxic and side effects. The invention provides a novel oral leukoplakia treatment means which has a good clinical application prospect.

The disclosure generally relates to Cathepsin S-sensitive linkers, short amino acid sequences attached to antigens that form a structure termed a hybrid peptide. Further disclosed are spherical nucleic acids (SNAs), nanostructures with a core surrounded by a shell of oligonucleotides, wherein in some embodiments the hybrid peptide is attached to one or more oligonucleotides in the shell of oligonucleotides. In some aspects, the disclosure provides a SNA comprising: (a) a nanoparticle core; (b) a shell of oligonucleotides comprising one or more oligonucleotides attached to the nanoparticle core; and (c) a hybrid peptide attached to one or more oligonucleotides in the shell of oligonucleotides, wherein the hybrid peptide comprises a Cathepsin S-sensitive linker and an antigen.

The application discloses a spherical nucleic acid preparation method based on a cyclic template strategy and application, and comprises the following steps: A) using controllable free radical polymerization (ATRP) and intramolecular click chemistry of copper-catalyzed alkyne and azido, a cyclic polymer is prepared c -P(HEMA) 30 B) using continuous esterification and substitution reaction, the cyclic polymer side chain terminal hydroxyl group is substituted by azido, and a cyclic template c -P(HEMA-N3) 30 C) using copper-free click chemistry reaction of a dibenzo cyclooctyne group (DBCO) and azido, nucleic acid is covalently coupled to the cyclic template, and a cyclic brush macromolecule c -P(HEMA-RNA) 30 The obtained cyclic brush macromolecule is subjected to water dialysis, and spherical nucleic acid is prepared through self-assembly. The spherical nucleic acid prepared by the preparation method has good reproducibility, good in-vitro stability, can better protect the nucleic acid from degradation of RNA degradation enzyme, and can greatly improve the nucleic acid uptake capacity of cells.

Liposomes termed as small unilamellar vesicles (SUVs), can be synthesized in the 20-50 nm size range, but encounter challenges such as instability and aggregation leading to inter-particle fusion. This limits their use as a therapeutic delivery agent. Increasing the surface negative charge of SUVs, via the attachment of anionic entities such as DNA / RNA, increases the colloidal stability of these vesicles. Additionally, the dense spherical arrangement and radial orientation of nucleic acids exhibits unique chemical and biological properties, unlike their linear counterparts. These liposomal particles, are non-toxic and though anionic, can efficiently enter cells without the aid of ancillary cationic transfection agents in a non-immunogenic fashion. These exceptional properties allow their use as delivery agents for gene regulation in different therapies and offer an alternative platform to metal core spherical nucleic acids.

The invention belongs to the field of research and development of tumor drugs, and provides a targeted albumin spherical nucleic acid drug for delivering a hydrophobic drug, aiming at solving the problems that the existing traditional albumin drug is poor in targeted enrichment, strong in systemic side effect and the like, and the targeted albumin spherical nucleic acid drug is characterized in that a hydrophobic molecule is wrapped in albumin (HSA), and meanwhile, the hydrophobic molecule is used as a spherical nucleic acid drug for delivering the hydrophobic drug. Albumin with a plurality of hydrophobic structural domains on the surface and a plurality of aptamer sequences (Apt) with hydrophobic groups at the 5'end are mutually non-covalently modified and combined through hydrophobic interaction to form a spherical nucleic acid structure, and the aptamer has specific targeting property. The invention also provides a preparation method and a use method of the spherical nucleic acid medicine. The drug provided by the invention has excellent targeting property and stability, can realize specific targeting delivery of different types of tumors, improves the treatment effect of the drug, reduces toxic and side effects, and is suitable for large-scale industrial application.

The application discloses a digital flow microsphere biochemical analysis method based on a spherical nucleic acid signal amplification mechanism and belongs to the technical field of protein and exosome marker detection. The application loads antibodies or aptamers on magnetic microspheres, and when the concentration of ultra-micro content targets is high, a single target marker molecule is specifically combined on the surface of one magnetic microsphere. The conversion efficiency of proteins or exosomes to nucleic acids is greatly improved by introducing functionalized spherical nucleic acids, a single target marker molecule on the surface of the microsphere triggers a large amount of nucleic acid amplification, and enough fluorescent signal is enriched to light the single magnetic microsphere, which is a positive microsphere. The magnetic microspheres without the target marker molecules cannot combine the functionalized spherical nucleic acids, trigger nucleic acid amplification and enrich the fluorescent signal, and are negative microspheres. Ordinary flow cytometers can obviously distinguish the positive microspheres from the negative microspheres, and the number of positive microspheres is counted to realize digital analysis of protein or exosome markers.

The invention discloses a preparation method and application of a spherical nucleic acid-based nanoprobe and a paper-based chip thereof. The preparation method is characterized by comprising the following steps: preparing the spherical nucleic acid nanoprobe based on a sulfadiazine aptamer by adopting a microwave method; the paper-based chip is prepared by constructing a hydrophobic barrier by adopting a laser printing and high-temperature heating method, a to-be-detected water sample is dropwise added into a sample adding area of the paper-based chip, and the sample firstly reaches a detection area 1 through capillary action and is gathered after acting with a nano probe for detecting aminoglycoside antibiotics, so that the color of the paper-based chip is changed; after the sample continuously flows to a detection area 2 and reacts with the prepared spherical nucleic acid nanoprobe based on the sulfadiazine aptamer, a sodium chloride solution is dropwise added into the area to trigger a particle aggregation reaction, so that the color of the paper-based chip is changed, and simultaneous detection of aminoglycoside and sulfonamide antibiotics is realized. Compared with the prior art, the method has the characteristics of rapidness, convenience, economy and practicability, and is of great significance to environmental risk assessment, pollutant control and public health.

The disclosure is generally related to calcium salted spherical nucleic acids (SNAs). SNAs comprise a nanoparticle core surrounded by a shell of oligonucleotides. In some aspects, the disclosure provides a spherical nucleic acid (SNA) comprising: (a) a nanoparticle core; and (b) a shell of oligonucleotides attached to the external surface of the nanoparticle core, wherein one or more oligonucleotides in the shell of oligonucleotides comprises a phosphate backbone; the SNA comprising Ca2+ ions adsorbed to the phosphate backbone of one or more oligonucleotides in the shell of oligonucleotides. Methods of making and using the SNAs are also provided herein.

The invention belongs to the technical field of biological medicine, and discloses a preparation method of bionic extracellular vesicle spherical nucleic acid and application of the bionic extracellular vesicle spherical nucleic acid to treatment of pulmonary fibrosis. Bionic extracellular vesicles are efficiently prepared through a mechanical extrusion method, the bottlenecks that natural EVs are low in yield, large in batch difference and the like are broken through, the obtaining efficiency of nano vesicles is remarkably improved, and the application range of the bionic extracellular vesicles to treatment of pulmonary fibrosis is widened. According to the present invention, the production cost is reduced, the bionic extracellular vesicle spherical nucleic acid (BEV-SNA) with the three-dimensional compact structure is formed through the efficient assembly of the cholesterol-modified single-chain DNA and the BEVs, the good biocompatibility and the good function superposition are provided, the bionic extracellular vesicle obtained through mechanical extrusion and the spherical nucleic acid are efficiently assembled to construct the multifunctional nanometer treatment platform, and the application prospect is broad. A new way for treating diseases such as pulmonary fibrosis is opened up.

The invention relates to a method for synthesizing spherical nucleic acid by reducing gold trichloride through alkynyl-modified DNA. The method comprises the following steps: preparing a gold trichloride aqueous solution, an alkynyl-modified DNA solution, a poloxamer 188 aqueous solution and an HEPES solution; adding a gold trichloride aqueous solution, an alkynyl modified DNA solution and a poloxamer 188 aqueous solution into an HEPES solution, and reacting to obtain the spherical nucleic acid of the DNA modified gold nanoparticles. According to the method, the alkynyl-modified DNA is used for reducing gold trichloride to synthesize the spherical nucleic acid in one step for the first time, the use of the alkynyl-modified DNA realizes rapid one-step synthesis of the DNA-modified gold nanoparticles, and the synthesis and modification processes of the spherical nucleic acid are greatly simplified. The preparation method is simplified, and the reaction time is shortened.

The application discloses an application of a multiplex miRNA fluorescence imaging method based on spherical nucleic acid and catalytic hairpin self-assembly in evaluation of DON and derivatives cytotoxicity, and belongs to the field of biological detection. The application first designs a catalytic hairpin self-assembly system for miR-155 and miR-210, and builds a fluorescence imaging method of miR-155 and miR-210 in macrophage RAW264.7 by taking spherical nucleic acid as a carrier of the catalytic hairpin self-assembly system. Further, the method is successfully applied to explore a dynamic change process of miR-155 and miR-210 in RAW264.7 cells in response to exposure of deoxynivalenol and acetylated derivatives thereof, thereby providing a theoretical basis and technical support for early toxicity screening of deoxynivalenol and derivatives thereof.

This invention discloses a quantum dot micelle spherical nucleic acid sensor, its preparation method, and its application in Pb 2+ In its detection application, the sensor comprises two nucleic acid molecules coupled to the surface of quantum dot micelles: an aptamer and an enzyme substrate modified with a quencher. The aptamer is formed by hybridization of a 5'-amino-modified lead ion aptamer with a DNase sequence. The enzyme substrate is a hairpin DNA structure containing an rA site, with an amino group modified at its 5' end and a quencher modified at its 3' end. The aptamer in this invention's sensor specifically binds to Pb. 2+ A G-quadruplex is formed, releasing DNase, which then travels automatically along its substrate-based pathway. By measuring the fluorescence signal of the quantum dot micelles after this travel is complete, the control of Pb is achieved. 2+ The detection and analysis of Pb. In this invention, QM-SNA-based DNase walking is used for Pb detection and analysis. 2+ The fluorescence amplification detection method realizes Pb detection 2+ Its high sensitivity and high specificity provide a new detection method for heavy metal ions.

The disclosure is generally related to cross-linked tumor lysate spherical nucleic acids (CLSNAs), nanostructures comprising a core to which a shell of oligonucleotides is attached. Methods of making and using the CLSNAs are also provided herein. In some aspects, the disclosure provides a cross-linked tumor lysate spherical nucleic acid (CLSNA) comprising: (a) a core comprising a plurality of cross-linked tumor cell antigens; and (b) a shell of oligonucleotides attached to the external surface of the core, the shell of oligonucleotides comprising one or more immunostimulatory oligonucleotides.

The disclosure is generally related to spherical nucleic acids (SNAs) comprising a protein corona, wherein the SNA comprises (i) a nanoparticle core and (ii) one or more oligonucleotides attached to the surface of the nanoparticle core, wherein the protein corona comprises a plurality of proteins. The disclosure also provides methods of using the same. The disclosure further provides methods of improving stability and / or extending blood circulation half-life of a spherical nucleic acid (SNA), the SNA comprising a nanoparticle core and one or more oligonucleotides attached to the surface of the nanoparticle core, the method comprising adsorbing a plurality of proteins on the surface of the SNA.

The invention discloses a triblock single-stranded nucleic acid, a spherical nucleic acid probe, preparation and application thereof and a virus detection test strip. The three-block single-stranded nucleic acid sequentially comprises an assembly structural domain, a hybridization structural domain and a report structural domain of which the tail end is coupled with biotin, and the single-stranded nucleic acid is adsorbed on the surface of the nano particle and forms a complementary double-stranded structure with the hybridization DNA to obtain the spherical nucleic acid probe. The method for detecting the virus by using the spherical nucleic acid probe comprises the following steps: designing and synthesizing crRNA by using a target sequence; carrying out incubation on the crRNA and CRISPR nuclease to construct a binary complex; mixing to-be-detected target nucleic acid or an isothermal amplification product thereof, the spherical nucleic acid probe and the binary complex for reaction to obtain to-be-detected liquid; a to-be-detected solution is dropwise added to the test strip, and interpretation is performed according to the color development conditions of the test line and the quality control line. The CRISPR gene editing technology is combined to realize rapid test paper mode detection of nucleic acid, and a simple, convenient, rapid and effective detection method is provided for disease prevention and control.

The present invention discloses a sensor for rapidly activating a CRISPR-Cas12a signal switch by target-triggered self-assembly of spherical nucleic acids, which relates to the technical field of biochemical analysis sensors, and includes a luminescent material and a sensor. The luminescent material is AuAgNCs@MOF-5, and a quenching probe modified with dopamine is on the surface of the material AuAgNCs@MOF-5. The sensor includes spherical nucleic acid A and spherical nucleic acid B. Both spherical nucleic acid A and spherical nucleic acid B are composed of a hairpin and a Y-shaped DNA nanostructure. The hairpin not only contains the recognition site of a DNAzyme dependent on Zn 2+ , but also contains an activator of CRISPR / Cas12a. The Y-shaped DNA nanostructure is composed of an auxiliary strand (APs), DNAzyme strands and an AMACR aptamer. The auxiliary strands of spherical nucleic acid A and spherical nucleic acid B are AP A and AP B respectively. The present invention can be used to detect the prostate cancer marker AMACR in serum samples, and can achieve highly sensitive and accurate detection of AMACR; it can solve the problems of low detection sensitivity and long time for detecting the prostate cancer marker AMACR in the prior art.

The disclosure is generally related to nanoparticles have an oxidized tumor cell lysate encapsulated therein and oligonucleotides on the surface thereof. Methods of making and using the nanoparticles are also provided herein.

Aspects of the invention relate to spherical nucleic acid-based constructs and related methods and compositions thereof. The compositions of the invention are useful for activating agonists of nucleic acid interacting complexes, such as TLRs, stimulating an immune response, and treating diseases such as infectious disease, cancer, allergies, allergic diseases, and autoimmune disease