41results about How to "Low immunogenicity" patented technology

The invention belongs to the field of skin care and skin disease treatment, and provides a skin care composition and application thereof, and the skin care composition is in a liquid form and comprises recombinant collagen and glycolic acid. The specific low-concentration glycolic acid in the skin care composition disclosed by the invention ensures the mild keratin metabolism capability; the recombinant collagen with high transdermal property can quickly permeate into the deep layer of the skin, and can immediately provide a repairing raw material for the skin while the glycolic acid acts, so that discomforts such as redness and stabbing pain are remarkably relieved, and synchronous skin care and repairing is realized.

This invention relates to a pH-responsive hydrogel composite dressing, its preparation method, and its application, belonging to the field of biomedical materials and drug delivery technology. The pH-responsive hydrogel composite dressing comprises a hydrogel matrix and engineered exosomes and platelet-rich plasma uniformly loaded within the hydrogel matrix. The hydrogel matrix comprises a three-dimensional dynamic cross-linked network formed by a Schiff base reaction between an amino-containing polysaccharide derivative and an oxidized aldehyde-containing polysaccharide derivative. The engineered exosomes are derived from donor cells subjected to pathogen-associated molecular pattern stress treatment. The dressing provided by this invention possesses both toxin capture and immunometabolic regulation functions, achieving synergistic therapeutic effects against MRSA-infected diabetic wounds.

The application provides an antibody against B7H6 and application thereof, the antibody comprising heavy chain variable region CDR1, CDR2 and CDR3 sequences shown in the amino acid sequences of SEQ ID NO: 1, 2 and 3 respectively or having at least 95% identity with SEQ ID NO: 1, 2 and 3; and / or light chain variable region CDR1, CDR2 and CDR3 sequences shown in the amino acid sequences of SEQ ID NO: 4, 5 and 6 respectively or having at least 95% identity with 4, 5 and 6. The antibody of the embodiment of the application can be combined with human and monkey B7H6 proteins, and the bispecific antibody prepared by using the antibody has higher human and monkey B7H6 binding activity, and can effectively treat and / or prevent B7H6-mediated related diseases.

The invention relates to a CD70 and BCMA targeting dual-targeting chimeric antigen receptor and an application thereof. The CD70 and BCMA targeting dual-targeting chimeric antigen receptor has specific binding ability to CD70 and BCMA. The immune effector cell prepared on the basis of the double-targeting chimeric antigen receptor has the following advantages that the probability that tumor cells escape treatment by losing a single antigen is greatly reduced, and the targeting treatment effect is improved; a CD70 nano antibody sequence is used, so that the length of an insertion fragment is greatly shortened, and the development difficulty of a process end is reduced; and the polypeptide has excellent proliferation capacity, is beneficial to prolonging the in-vivo duration time, and plays a more remarkable anti-tumor role. The invention provides a treatment or improvement approach for diseases related to BCMA-CD70 expression.

This invention belongs to the field of biotechnology, specifically relating to a high-affinity anti-tumor NK cell, its preparation method, and its application. This invention designs NK92 cells transfected with a haPD1 high-affinity chimeric conversion receptor, wherein the high-affinity chimeric conversion receptor includes the extracellular segment of haPD-1, the transmembrane segment of CD28, the intracellular segment of DAP10, and the intracellular segment of CD3ζ. This invention prepares haChR3-NK92 cells through the construction of a recombinant lentiviral vector, lentiviral packaging, and lentiviral transfection of NK92 cells. In this invention, haPD-1 serves as the extracellular recognition domain of the CAR structure, specifically binding to PD-L1 on tumor cells to achieve a stronger tumor-killing effect. The co-stimulatory molecule CD28 serves as the transmembrane region to transmit extracellular information into the cell, integrating the adaptor protein DAP10 of the NK cell surface activator receptor NKG2D into the cell, and further embedding the intracellular segment CD3ζ commonly used in CAR design to jointly promote NK cell activation. The preparation method of this invention can successfully construct haChR3-NK92 cells, achieve the expression of the target plasmid, and be applied in anti-tumor drug research.

The invention relates to the technical field of immunity, in particular to a nano antibody specifically combined with CD276 and application of the nano antibody. The preparation method comprises the following steps: immunizing alpaca by adopting human CD276 antigen protein to obtain peripheral blood PBMC (peripheral blood mononuclear cell), then calling a nano antibody gene, establishing a phage library, finally obtaining an antibody sequence with relatively high antigen affinity respectively through a single B cell antibody screening technology and a phage library screening technology, and then applying the found antibody sequence to CAR-T to obtain a CAR-T antibody sequence with relatively high antigen affinity. Animal in-vivo and in-vitro drug effects show that the obtained antibody sequence is suitable for various solid tumor indications and has a remarkable anti-tumor effect on lung cancer, colorectal cancer and pancreatic cancer. The antibody sequence can be applied to development of antibody drugs, cell therapy drugs, ADC drugs and the like.

The invention belongs to the technical field of medical dressings, and relates to a DNA hydrogel dressing with a skin-like structure and function as well as a preparation method and application of the DNA hydrogel dressing. The dressing is structurally characterized in that a skin-like three-layer structure, namely an epidermal layer, a corium layer and a subcutaneous tissue layer, is constructed by regulating and controlling the cross-linking degree of chain segments and combining a directional freezing technology, and an extracellular matrix microenvironment is provided for physiological activities of cells. In function, an aptamer sequence with a specific function is introduced, and stem cells are induced to directionally differentiate into cells required by tissue repair; the subcutaneous tissue-like layer is loaded with resveratrol, and fascia is activated to induce regeneration of skin appendages; in view of the fact that chronic ulcerative wounds are easily attacked by bacteria, the antibacterial peptide and a functional DNA sequence of targeted bacteria form an antibacterial peptide-DNA composite chain segment through a click reaction, and the dressing is endowed with targeted antibacterial performance. The prepared dressing has a skin-imitating three-dimensional structure and performance, can guide skin appendages such as regeneration of hair follicles and sweat glands, and can be widely applied to repair treatment of chronic wounds.

The present application provides an anti-TIGIT antibody or an antigen-binding fragment thereof specifically binding to TIGIT, a composition comprising the anti-TIGIT antibody or the antigen-binding fragment thereof, and use thereof in diagnosis and treatment of TIGIT-related diseases.

The invention discloses a preparation method and application of ganoderma lucidum outer vesicles without sporocarp waste sources. The ganoderma lucidum external vesicles are used for preparing medicines for treating ischemic cerebral apoplexy sequelae, and can improve core symptoms such as dyskinesia (including limb paralysis, imbalance and gait abnormity), cognitive decline and the like after apoplexy. The spore-free sporocarp waste sourced ganoderma lucidum outer vesicles are prepared from spore-free sporocarp waste which is completely released by spores after a ganoderma lucidum powder spraying period through raw material pretreatment, differential centrifugation, tangential flow concentration and filter membrane filtration. According to the preparation method, the waste is used as a raw material to prepare the high-value medical outer vesicle, green circulation of agricultural waste-high-added-value medical raw materials is achieved, the ganoderma lucidum outer vesicle can effectively penetrate through the blood-brain barrier, brain-targeted delivery is achieved, and the problems that traditional ganoderma lucidum active ingredients are low in blood-brain barrier penetration rate and poor in blood-brain barrier penetration rate are solved. The effective treatment concentration in the brain tissue is difficult to achieve, and the traditional drug delivery bottleneck is broken through.

This invention relates to the field of biomedical technology, and more particularly to a PD-L1-targeting polypeptide, its conjugate, and its applications. The polypeptide possesses the amino acid sequence shown in SEQ ID NO.1 or SEQ ID NO.2. This invention de novo designs a high-affinity PD-L1-targeting specific polypeptide. This polypeptide achieves extremely high affinity with the extracellular domain of the PD-L1 protein through its unique spatial conformation, exhibiting excellent targeting and recognition capabilities. The polypeptide provided by this invention can be conjugated with various modified molecules, such as radionuclides, and the constructed molecular imaging probe exhibits excellent tumor tissue targeting and enrichment capabilities, superior biocompatibility, and clear imaging contrast, enabling specific recognition of PD-L1-positive tumor lesions. It can be applied to clinical scenarios such as early precision diagnosis of tumors, screening of patients for immunotherapy, real-time monitoring of efficacy, and prognostic assessment, possessing significant translational medical value and broad application prospects.

This invention discloses a nanobody Nb.TB1, engineered plant exosomes, their preparation methods, and applications, belonging to the field of biomedical technology. The amino acid sequence of the nanobody Nb.TB1 is shown in Seq ID No. 1. Furthermore, this invention proposes a method for preparing engineered plant exosomes, comprising the following steps: S1, extraction of Gastrodia elata exosomes: extracting Gastrodia elata exosomes from Gastrodia elata using an enzymatic method; S2, expression and purification of the blood-brain barrier-crossing nanobody fusion protein with Sortase A ligase; S3, surface modification of the Gastrodia elata exosomes. In addition, this invention also proposes an engineered plant exosome prepared by the above method. Furthermore, this invention proposes the application of the above-mentioned engineered plant exosomes in the preparation of targeted therapeutic drugs for central nervous system diseases. The engineered plant exosomes prepared by this invention exhibit high blood-brain barrier crossing efficiency.

This invention discloses an extracellular vesicle derived from Sophora flavescens, its preparation method, and its application. It belongs to the field of biomedical technology. The extracellular vesicles derived from Sophora flavescens are obtained by isolating extracellular vesicles (SF-EVs) from the roots of Sophora flavescens. These vesicles have a particle size of 100-200 nm and contain proteins, lipids, high abundance of miR6300, and various alkaloids. This invention also provides a method for preparing the extracellular vesicles and further provides their application in the preparation of drugs for treating metabolic-associated steatohepatitis (MASH). In vitro and in vivo experiments have demonstrated that SF-EVs can significantly improve lipid accumulation, inflammatory response, and oxidative stress in MASH, with an overall therapeutic effect superior to an equivalent dose of total alkaloids from Sophora flavescens. Through protein / RNA knockout, transcriptome sequencing, and mechanism verification, miR6300 was found to be a key effector of SF-EVs in its anti-MASH effect, and it exerts a synergistic therapeutic effect by dually targeting CYP2B6 (improving lipid metabolism) and CXCL10 (inhibiting inflammation).

This disclosure pertains to the field of biomedicine, specifically relating to double-stranded oligonucleotides targeting the APP gene and their applications. Specifically, it provides double-stranded oligonucleotide agents or their salts, conjugates, or compositions for inhibiting amyloid precursor protein (APP) expression, wherein the double-stranded oligonucleotide agent comprises a sense strand and an antisense strand forming a double-stranded region; wherein the antisense strand sequence comprises at least 15 consecutive nucleotides of any of the sequences shown in SEQ ID NO:1-154 with a difference of no more than 3 nucleotides, and / or the sense strand sequence comprises at least 15 consecutive nucleotides of any of the sequences shown in SEQ ID NO:155-308 with a difference of no more than 3 nucleotides. The double-stranded oligonucleotide agent or its salt for inhibiting APP expression disclosed in this application can significantly inhibit APP expression and can be used for the prevention and / or treatment of diseases or conditions mediated by the APP gene and / or associated with protein amyloidosis.

The invention provides a method for allele matching of donor mesenchymal stem cells and a receptor. The method comprises the following steps: S10, separating mesenchymal stem cells from perinatal tissue of a donor; s20, extracting genome DNA (deoxyribonucleic acid) of the mesenchymal stem cells, and performing HLA (human leukocyte antigen) genetic typing; s30, performing HLA (human leukocyte antigen) genetic typing on the DNA of the receptor; s40, performing allele spectrum comparison on the HLA gene of the receptor and the HLA gene of the mesenchymal stem cell, and calculating the matching degree; s50, judging the matching degree of the receptor and the mesenchymal stem cells according to the matching degree; and S60, storing the HLA genotyping result of the mesenchymal stem cells and the matching degree in a database, and establishing a matching library for matching the donor mesenchymal stem cells and the receptor. According to the method, a set of standardized system is established, compatibility evaluation of a donor and a receptor at the allele level is achieved, the immunological rejection risk caused by HLA mismatching is effectively predicted and avoided before treatment, and the in-vivo survival and implantation efficiency of MSCs is improved.

The invention belongs to the technical field of biological medicines, and discloses a single-domain antibody for detecting CD28, and the amino acid sequence of the single-domain antibody is as shown in SEQ ID No.1. The antibody has good reaction activity with human CD28, can be used for detecting or diagnosing CD28 and treating related diseases with abnormal expression of CD28, and provides a basis for research and development of drugs targeting CD28.

The invention discloses application of retinoic acid or a derivative thereof in preparation of a medicine for promoting healing of a tooth extraction wound. It is found that retinoic acid can promote proliferation of mesenchymal cells in the tooth extraction wound and differentiation of hard tissue, so that rapid healing of the tooth extraction wound is promoted, the healing period of the tooth extraction wound is shortened, and early complications of healing of the tooth extraction wound are reduced.

This invention belongs to the field of biomedical technology and discloses a chimeric antigen receptor targeting CD20, its gene expression construct, and its applications. The chimeric antigen receptor provided by this invention specifically includes an amino acid fragment with the sequence shown in SEQ ID NO:29 or a variant fragment having at least 85% sequence identity with SEQ ID NO:29. Its functional fragments, including the signal peptide, antigen-binding region, hinge region, transmembrane region, intracellular co-stimulatory domain, and signal transduction domain, form an organic whole, working synergistically to endow the chimeric antigen receptor with good CD20-targeting binding, T-cell activation, and cell-killing effects, demonstrating excellent application potential in the preparation of drugs for the treatment of relapsed / refractory B-cell malignancies.

This invention relates to the fields of biomedical engineering and drug delivery technology, specifically disclosing a novel targeted drug delivery system based on rosehip extracellular vesicles, comprising: preparing rosehip-derived extracellular vesicles; preparing drug-loaded vesicles; and preparing targeted modified drug-loaded vesicles. This invention utilizes the specific downregulation of stem cell-related pathways by rosehip components, while simultaneously leveraging doxorubicin to kill conventional tumor cells, forming a complementary therapeutic mechanism to fundamentally reduce the risk of tumor recurrence. The phenylboronic acid group of DSPE-PEG-PBA specifically recognizes sialic acid overexpressed on the surface of tumor cells, significantly increasing drug accumulation in tumor tissues while reducing distribution in normal tissues. By leveraging the natural biocompatibility and low immunogenicity of RHNVs, combined with the long-circulating properties of the PEG chain, systemic toxicity is minimized while ensuring delivery efficiency, particularly reducing the cardiotoxicity and bone marrow suppression of doxorubicin.

This invention provides an aptamer targeting the growth hormone receptor and its uses, the nucleotide sequence of which is shown in SEQ ID NO.1 or SEQ ID NO.2. This invention utilizes a modified SELEX technique to perform multiple rounds of screening targeting recombinant GHR protein, obtaining specific nucleic acid aptamers with high affinity for GHR (KD values ​​at the micromolar level). In vivo distribution experiments show that the fluorescently labeled aptamer can efficiently and specifically accumulate in white adipose tissue (including inguinal and gonadal fat) at the in vivo level, exhibiting excellent tissue targeting. The nucleic acid aptamer and its derivatives of this invention can be used to prepare drugs or diagnostic reagents targeting adipose tissue, for example, for the prevention or treatment of metabolic diseases such as obesity, type 2 diabetes, fatty liver, hyperlipidemia, or cardiovascular disease.

This invention belongs to the field of genetic engineering technology and discloses a method for synthesizing mussel adhesive protein using gene recombination technology, as well as related recombinant vectors and strains. The method uses the core functional genes of mussel byssalin 3 and 5 as templates, and constructs a recombinant expression vector pET-20b-fp-cut through artificial synthesis and overlapping PCR gene tandem. This vector is then transformed into *E. coli* BL21 to obtain the recombinant strain BL21 / pET-20b-fp-cut. A gradient-scale fermentation process is used to optimize the efficient expression of the target protein. The product is then extracted using a salting-out-acetic acid extraction combined with tyrosinase-catalyzed purification process. Finally, multi-dimensional quality testing is used to verify the indicators. This invention also provides the aforementioned recombinant expression vector and recombinant strain. This method can realize the industrial production of mussel adhesive protein, with a fermentation unit of 5.2 g / L, a dopa content of 11.2%, and a purity of 96.5%. It also exhibits low immunogenicity and meets quality standards, showing broad application prospects in biomedicine, cosmetics, and other fields.

The invention relates to the technical field of biological medicine, in particular to a bicyclic peptide ligand aiming at GPC3, a pharmaceutical composition and application of the bicyclic peptide ligand. The bicyclic peptide ligand provided by the invention has high binding affinity and specificity with the GPC3 protein, and can effectively realize recognition and targeting of the GPC3 protein. Compared with an antibody inhibitor, the bicyclic peptide inhibitor has significantly lower immunogenicity and can effectively reduce side effects. The bicyclic peptide ligand provided by the invention can be used as a tool for researching the action of the GPC3 protein in the physiological process, can be used as a candidate targeting molecule of an anti-tumor drug, and is used for the scenes of early diagnosis, prevention, treatment and the like of HCC and other tumors.

This invention discloses a collagen-based anti-corrosion coating with tissue repair properties, its preparation method, and its applications, belonging to the field of medical coating technology. This invention designs a novel self-healing anti-corrosion coating and loads collagen onto the coating using excipients, achieving a deep integration of anti-corrosion protection and biological function. The prepared collagen-based anti-corrosion coating is firmly bonded to a magnesium alloy substrate via covalent bonds. After 4 weeks of in vivo implantation, no cracking or detachment was observed, the stent structure maintained good integrity, and it provides continuous radial support, offering sufficient time for vascular repair. This provides a feasible solution for the clinical translation of next-generation biodegradable magnesium-based vascular stents.

The invention provides a composition for filling as well as a preparation method and application thereof. The composition comprises gel particles and an aqueous medium hyaluronate solution, the gel particles comprise silk fibroin, hyaluronic acid or a salt thereof, and a cross-linking agent, and the gel particles comprise a porous three-dimensional body; the mass ratio of the silk fibroin to the hyaluronic acid or the salt thereof to the cross-linking agent is (0.1-10): (1-20): 1.

The invention discloses an mRNA (messenger ribonucleic acid) delivery system based on a nucleic acid nanostructure as well as a preparation method and application of the mRNA delivery system. The mRNA delivery system comprises an mRNA scaffold chain, an RNA staple chain, a lipid-nucleic acid coupling chain and an auxiliary lipid; the mRNA scaffold chain comprises a nucleic acid sequence for coding target protein mRNA; the mRNA scaffold chain and the RNA staple chain are self-assembled through complementary base pairing to form a nucleic acid nanostructure; the lipid-nucleic acid coupling chain comprises a lipid molecule and a nucleic acid chain coupled with the lipid molecule. According to the invention, mRNA molecules of coding functional protein are used as scaffold chains to be accurately integrated into the nucleic acid nanostructure, so that the purpose of protecting and delivering mRNA is achieved, and the effect of accurately regulating and controlling the expression of target protein is achieved.

The invention relates to the technical field of stem cell engineering and anti-aging biology, in particular to a histone modification regulation method based on placenta amnion sub-totipotent stem cells and an anti-aging preparation thereof. The regulation and control method comprises the following steps: separating and purifying healthy full-month caesarean section placenta amniotic membrane tissues, carrying out composite enzymolysis and flow cytometry screening to obtain CD105 < + >, CD73 < + > and CD45 <-> stem cells, and primarily culturing the CD105 < + >, CD73 < + > and CD45 <-> stem cells; the method comprises the following steps: determining histone methyltransferase MLL3 and demethylase JMJD3 as target spots through ChIP-seq, and determining H3K4me3 and H3K27me3 as target modification sites; an MLL3 activator CM-272 with the final concentration of 15 [mu] M and a JMJD3 inhibitor GSK-J4 with the final concentration of 10 [mu] M form a composite regulator, and induction culture is performed for 84 h under the conditions of 37 DEG C and 5% CO2; and carrying out Western Blot verification and screening on the stem cells meeting the standard. According to the anti-aging preparation, regulated stem cells are used as active ingredients, a sodium alginate-gelatin (2: 1) composite carrier, 5% mannitol and 1% human serum albumin protective agent are used as auxiliary materials, and the injection with the pH of 7.2-7.4 is prepared. The method is accurate in regulation and control, and the preparation is remarkable in anti-aging effect and low in immunological rejection risk.

Provided are anti-IL-4R [alpha] antibodies or antigen binding fragments thereof, anti-TSLP antibodies or antigen binding fragments thereof, antigen binding protein constructs (e.g., multispecific or bispecific antibodies capable of specifically binding IL-4R [alpha] and TSLP). Polynucleotides encoding the antibody or antigen binding protein constructs, as well as expression vectors and host cells comprising the same, are provided. Also provided are immunoconjugates, pharmaceutical compositions, and medicaments, as well as their use in the treatment of immune disorders, such as type II or hybrid allergic diseases.

The application belongs to the technical field of synthetic biology, and particularly relates to a recombinant I&III fusion type collagen with high stability and low immunogenicity, and a preparation method and application thereof. The amino acid sequence of the recombinant I&III fusion type collagen and the nucleotide sequence of the coding gene thereof are disclosed. The recombinant I&III fusion type collagen with high stability and low immunogenicity is prepared by a fermentation method of an engineering bacterium. The results of examples show that the recombinant I&III fusion type collagen colI&III-1 provided by the application has good thermal stability, long-term stability and anti-degradation capacity. The animal experiment proves that the recombinant I&III fusion type collagen colI&III-1 has low immunogenicity, and does not cause immune balance disorder of animals. In addition, the recombinant I&III fusion type collagen has the characteristics of high biocompatibility and good safety, and has no influence on the overall health condition of animals.

This invention provides a nucleic acid aptamer that binds to the Spike protein of the novel coronavirus SARS-CoV-2 and its applications. The nucleic acid aptamer includes the nucleotide sequence shown in SEQ ID NO 1, 2, or 3; the nucleic acid aptamer, its combinations, and derivatives can specifically bind to the Spike protein of SARS-CoV-2 (wild-type or mutant), blocking the interaction between the Spike protein and the TLR4 protein, and inhibiting the inflammatory response triggered by SARS-CoV-2 virus infection; it has advantages such as high affinity, strong stability, small molecular weight, and low immunogenicity; this invention can be applied in the fields of detection, labeling, imaging, diagnosis, and treatment of the novel coronavirus.

The application belongs to the technical field of biological detection and antibody engineering, and particularly relates to a nanobody for detecting tomato brown rugose fruit virus and a preparation method and application thereof. The application discloses a specific nanobody for detecting tomato brown rugose fruit virus and application thereof. Complementarity determining region sequences of the nanobody are shown in SEQ ID NO: 4-6; and a complete variable region amino acid sequence of the nanobody is shown in SEQ ID NO: 1. The application simultaneously provides a nucleotide sequence for encoding the nanobody, a recombinant expression vector, a host cell and a preparation method thereof. The nanobody has high affinity and excellent thermal stability to ToBRFV coat protein, and has no cross reaction with TMV, ToMV and other related viruses. A detection kit and a colloidal gold test strip constructed based on the antibody have a detection limit of 10 pg / mL, and are suitable for rapid screening and field quantitative diagnosis of ToBRFV.

This invention belongs to the field of antibody technology, specifically relating to an IL13Rα2 nanobody targeting IL13Rα2, a chimeric immune receptor, and their applications and products. This invention is the first to discover an IL13Rα2 nanobody with a specific complementarity-determining region amino acid sequence. The nanobody possesses advantages such as high affinity, high specificity, low immunogenicity, small molecular weight, and strong tissue penetration. This invention also provides a chimeric immune receptor comprising the nanobody, recombinant protein, nucleic acid molecule, expression vector, engineered immune cells, antibody preparation, kit, and pharmaceutical composition. CAR-T cells constructed based on the nanobody exhibit highly efficient and specific killing ability against IL13Rα2-positive tumor cells and can effectively overcome tumor antigen heterogeneity. They can be used to prepare drugs or kits for the diagnosis or treatment of IL13Rα2-related diseases, showing promising clinical application prospects.