2570 results about "Binding domain" patented technology

Compositions of retroviruses and methods of using the same for gene delivery are disclosed, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

Compositions and methods relating to paraoxonase fusion polypeptides are disclosed. In some aspects, the fusions are bispecific molecules that include a first biologically active polypeptide linked amino-terminal to a biologically active paraoxonase, wherein the first biologically active polypeptide is a DNase, an RNase, a SOD1, a CTLA-4 extracellular domain, a CD40 extracellular domain, or a polypeptide that specifically binds and neutralizes an inflammatory cytokine. Bispecific fusions may further include a second biologically active polypeptide (e.g., a dimerizing or FcRn-binding domain) linked carboxyl-terminal to the first biologically active polypeptide and amino-terminal to the paraoxonase. In other aspects, a fusion polypeptide includes a biologically active paraoxonase linked carboxyl-terminal or amino-terminal to a dimerizing or FcRn-binding domain. Also disclosed are dimeric proteins comprising first and second paraoxonase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Provided herein are binding molecules comprising a human neonatal Fc receptor (FcRn) binding molecule and at least one antigen-binding domain linked to the FcRn binding molecule. Polynucleotides, vectors, host cells, and methods of production are also provided herein. Methods of treating an antibody-mediated disorder with an FcRn / antigen-binding molecule are further provided.

The present disclosure provides humanized antibodies and antigen binding domains thereof that bind CD8α and other antibody formats comprising these antigen binding domains, their use as a targeting moiety on lipid nanoparticles (tLNP) to deliver a therapeutic payload (such as a nucleic acid molecule) or other types of payloads. The present disclosure further relates to pharmaceutical compositions comprising the humanized anti-CD8α antibodies and CD8-targeted tLNP encapsulating a payload.

The invention discloses a protein optimization design and screening method and device based on an artificial intelligence algorithm, and the method takes fungal luciferase as an example, and integrates multi-dimensional bioinformatics analysis and deep learning technology to realize efficient protein engineering transformation and optimization. The method comprises the following steps: firstly, identifying a binding domain of luciferase and fluorescein by utilizing an AI-driven molecular docking simulation method, and determining a key conservative site by combining literature, evolutionary analysis and structural prediction; then, generating a protein functional domain skeleton under the constraint of a fixed site by adopting a diffusion model, and performing protein sequence prediction by utilizing a graph neural network model; and finally, scoring and screening the generated sequences to obtain high-stability candidate variants. According to the method, a conservative site dynamic fusion strategy is innovatively constructed, a fixed region is optimized through logic of structure prediction, evolution site intersection priority and literature site union set expansion, the diversity and adaptability of a protein design sequence are met, and the efficiency bottleneck of a traditional scheme is broken through.

The invention discloses a fatty acid modified coronavirus antigen and application thereof, and belongs to the field of biological medicine. The fatty acid modified coronavirus antigen contains fatty acid modified N-terminal cysteine (Cys) and a coronavirus antigen, and can contain a connecting structural domain; the coronavirus antigen is a coronavirus spike protein (S protein) receptor binding domain (RBD). The fatty acid modified coronavirus S protein RBD can be self-polymerized into nanoparticles, and compared with the RBD which is not subjected to fatty acid modification, the antigen can induce faster and higher humoral immunity through injection immunity, can induce mucosal immunity and humoral immunity through respiratory tract atomization immunity, and is a candidate mucosal vaccine with potential medical value.

Provided herein is a system for inhibiting a miRNA-17 family miRNA from binding to the 3'UTR of PKD1, where the system includes: a gRNA; and a polynucleotide-programmable nucleotide-binding domain, where the system modifies a binding site of a miRNA-17 family miRNA in the 3'UTR of PKD1, thereby preventing binding of the miRNA-17 family miRNA and de-repressing PKD1 mRNA.

The invention discloses a CA9-targeted chimeric antigen receptor and application thereof, and belongs to the technical field of biological medicines. The CA9 targeting chimeric antigen receptor provided by the invention comprises a CD8 alpha leading signal peptide, an anti-CA9 single-chain variable fragment, a CD8 alpha hinge, a CD8 transmembrane structural domain and a CD3 zeta intracellular costimulatory signal transduction structural domain. According to the invention, an anti-CA9 single-chain variable fragment is used as an antigen binding structural domain to construct a chimeric antigen receptor (CAR) molecule, the macrophage expressing the anti-CA9CAR can realize specific targeting and phagocytosis killing of CA9 positive kidney cancer cells, and the constructed lipid nanoparticle delivery system can effectively transfer a gene expression vector, so that the gene expression vector can realize effective target site delivery, and the CA9 positive kidney cancer cells can be effectively targeted and killed. The constructed hydrogel-liposome combined drug delivery system has the performance of relieving toxic and side effects, controllable release and hemostasis.

The invention belongs to the technical field of biology, and provides a nanometer antibody targeting Nectin-4, and a nucleic acid molecule and an expression vector for coding the nanometer antibody targeting Nectin-4. The invention also provides a chimeric antigen receptor which comprises an extracellular antigen binding domain, a transmembrane domain and an intracellular domain, and the extracellular antigen binding domain is a Nectin-4 nano antibody; the invention also provides a chimeric antigen receptor CAR which contains the nano antibody as scFv and co-expresses CXCR1, a CAR-T cell constructed by the chimeric antigen receptor CAR, and an enhanced CAR-T cell obtained by modifying the CAR-T cell with microbial short-chain fatty acid, so as to improve the infiltration and anti-tumor activity of the CAR-T cell targeting Nectin-4.

The present disclosure provides inter alia, molecules comprising a binding domain that binds specifically to a target antibody and at least one modified Fc domain. The present disclosure also provides methods and compositions that allow for selective depletion and / or neutralization of pathogenic antibodies.

The present disclosure provides inter alia, molecules comprising an autoantibody-binding domain and at least one modified Fc domain. The present disclosure also provides methods and compositions that allow for selective depletion and / or neutralization of pathogenic autoantibodies.

The invention relates to the technical field of biological medicine, and provides a targeting exosome capable of delivering nucleic acid drugs and a preparation method of the targeting exosome. The exosome comprises a fusion polypeptide, the fusion polypeptide comprises a targeting protein molecule, an exosome transmembrane protein and a nucleic acid binding domain, and the exosome can load a nucleic acid molecule through binding of the nucleic acid binding domain. According to the invention, engineering modification is carried out on the exosome, so that nucleic acid molecules can be efficiently loaded into the exosome, and meanwhile, the exosome is endowed with the capability of targeting to specific target cells, tissues and organs.

The invention discloses a fusion protein and application thereof. Fusion expression is carried out on R ring binding domains from different species sources and a single gene base editor, and it is found that compared with a base editor before fusion, the base editing efficiency of the obtained fusion protein is improved, and a base editing window is widened. According to the method, the R-ring binding structure domain is fused with the single-gene base editor, so that the base editing efficiency can be improved, and an editing window can be adjusted, so that the method can be suitable for more base editing scenes. The method is beneficial to popularization and application of a single-gene editing technology, and has wide application prospects in prevention and / or treatment of diseases and construction of animal models or plant varieties.

The invention discloses a function-enhanced recombinant fibronectin as well as a preparation method and application thereof. The amino acid sequence of the recombinant fibronectin is shown as SEQ ID No.3, and the recombinant fibronectin is formed by fusing a main structural domain FN III8-10 formed by combining human fibronectin mutated into proline at the 171st site with integrin and a main structural domain FN III12-14 formed by combining the human fibronectin with cell factors. The recombinant fibronectin provided by the invention has enhanced cell proliferation and adhesion promoting performance of human fibroblasts, shows excellent cell biological efficacy, can be efficiently expressed in pichia pastoris engineering strains, and has wide application prospects in the fields of skin care, beauty and tissue engineering.

The present disclosure provides inter alia, molecules comprising an autoantibody-binding domain and at least one modified Fc domain. The present disclosure also provides methods and compositions that allow for selective depletion and / or neutralization of pathogenic autoantibodies.

Disclosed herein are compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

Provided are methods of generating chimeric antigen receptors (CAR). In some embodiments, library screening of CAR is performed by generating a vector encoding the CAR from random attachment of vectors from libraries of vectors encoding antigen-binding domains (e.g., scFv regions), hinge regions, and endodomains. In some embodiments, the vectors contain a transposon.

Provides herein are molecules or multifunctional molecules comprising an antigen binding domain that binds to a T cell receptor beta variable region (TCRβV) and a cytokine molecule, and methods of treating conditions or diseases in a subject using the same.

The present invention relates to a device comprising at least one reaction space with a single pre-dispensed dried reagent composition suitable for performing an assay method for detecting at least one analyte in a sample to be added to the reaction space, wherein the reagent composition comprises at least one set of analyte-specific proximity probes and a drying stabiliser, wherein the proximity probes in the set each comprise a binding domain for binding directly or indirectly to the analyte and a nucleic acid domain. The invention further relates to a method of performing a detection assay with use of the device, as well as a method of preparing the device.

The invention provides a system for evaluating an ADE effect in vitro and application of the system. The system comprises: (i) and (iii); (ii) and (iii); or (i), (ii) and (iii); in one embodiment, the present invention relates to a cell comprising: (i) an SARS-CoV-2 pseudovirus, (ii) an antibody that targets the receptor binding domain of SARS-CoV-2, and (iii) a cell that overexpresses CD32B; the cells are CHO cells. The system provided by the invention can be used for evaluating the ADE effect of the to-be-detected SARS-CoV-2 or the pseudovirus prepared from the to-be-detected SARS-CoV-2 or the antibody targeting the SARS-CoV-2, and has the advantage of higher sensitivity compared with a system based on cells expressing CD32A. The ADE evaluation system has a wide detection range, and can evaluate the ADE effect caused by the action of the SARS-CoV-2 virus or the pseudovirus prepared from the SARS-CoV-2 virus on CHO-CD32B in the presence of the RBD antibody with a wide concentration range (16 ng / mL-10000 ng / mL).

This invention relates to recombinant nucleic constructs comprising a DNA binding domain, an endonuclease and a reverse transcriptase and methods of use thereof for modifying nucleic acids in plants.

Provided are a bispecific antibody, a drug conjugate thereof, and a use thereof. The bispecific antibody comprises an EGFR binding domain and an HER3 binding domain. The provided bispecific antibody and the drug conjugate thereof have excellent endocytosis effects, proliferation inhibition activity and tumor growth inhibition activity, as well as good in vivo safety.

Provided herein are engineered Cas13 proteins with enhanced collateral activity. The engineered proteins comprise RNA binding domains (RBDs) fusions within an active site-proximal loop within a higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain. Also provided are compositions comprising and methods of using the engineered Cas13 proteins to detect target nucleic acids at attomolar sensitivity.

Provided is a recombinant human serum albumin-collagen binding domain (CBD) fusion protein for tumor-specific targeting matrix and its use in specific targeted treatment of a solid tumor. HSA and the CBD generate gene fusion in the form of different molecular structures, and can be expressed in a constructed recombinant engineered host. A pharmaceutical recombinant fusion protein is obtained through large-scale fermentation. The recombinant fusion protein shows tumor-specific targeting of solid tumors and can be used as a starting material of a broad-spectrum matrix carrier. The recombinant fusion protein is coupled with any tumor treatment drug, small-molecule compound, or cytotoxic protein to form an innovative pharmaceutical composition. The pharmaceutical composition of the recombinant fusion protein is also long-acting, can prolong a half-life of the conjugate drug in vivo, and has a significantly better clinical curative efficacy on anti-tumor than that of a monomer drug.

The invention discloses preparation and application of a targeting LYPD3 chimeric antigen receptor T cell. The chimeric antigen receptor comprises an LYPD3 antigen binding domain, a transmembrane domain, a costimulatory signal transduction domain and an intracellular signal transduction domain, the LYPD3 antigen binding domain comprises a heavy chain variable region with CDR-H1, CDR-H2 and CDR-H3 and a light chain variable region with CDR-L1, CDR-L2 and CDR-L3, and the CDR-H1, the CDR-H2 and the CDR-H3 are respectively composed of amino acid sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5. And the CDR-L1, the CDR-L2 and the CDR-L3 are respectively composed of amino acid sequences as shown in SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

The invention belongs to the technical field of biological medicine, and particularly discloses an antibody targeting ADAM17 protein and application of the antibody. The invention provides the ADAM17 specific target spot aiming at the malignant tumor of the biliary tract, the ADAM17 is highly expressed in the tumor of the biliary tract and is relatively low in expression in normal tissues, and by intervening the target spot, tumor cells can be killed, and non-specific attack to normal cells can be avoided as much as possible, so that the effectiveness and the safety of treating a patient with the malignant tumor of the biliary tract are improved. The invention also provides an antibody targeting ADAM17 protein and a preparation and screening method thereof, and the antibody can specifically recognize an antigen binding domain of ADAM17, has strong affinity with an ADAM17 antigen, and can be used for treating ADAM17 positive malignant tumors.

A bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. A nucleic acid comprising a polynucleotide encoding the antibody construct, a vector comprising the nucleic acid comprising the polynucleotide and a host cell transformed or transfected with the nucleic acid comprising the polynucleotide or vector. A process for the production of the antibody construct, a medical use of the antibody construct in the treatment of melanoma, and a kit comprising the antibody construct.

The invention discloses a system for evaluating an ADE effect and application thereof. The system comprises: (i) and (iii); (ii) and (iii); or (i), (ii) and (iii); (i) is a Middle East Respiratory Syndrome Coronavirus pseudovirus, (ii) is an antibody that targets the receptor binding domain of the Middle East Respiratory Syndrome Coronavirus, and (iii) is a cell that overexpresses CD32B; the cells are CHO cells; the pseudovirus contains a Spike protein coding gene of the Middle East Respiratory Syndrome Coronavirus. According to the invention, the ADE activity of the Middle East respiratory coronavirus antibody is identified in vitro by using MERS-CoV pseudovirus and cells for exogenous expression of CD32B. Compared with an immune cell Raji and an ADE evaluation system based on exogenous expression CD32A cells, the system provided by the invention is more sensitive, and is a potential system for evaluating the ADE effect of the Middle East respiratory coronavirus.

The invention discloses a double-structural-domain recombinant human fibronectin, the sequence of which is shown as SEQ ID NO.3, and the double-structural-domain recombinant human fibronectin is formed by fusing a collagen binding structural domain and a cell binding structural domain of human fibronectin. The invention also provides a recombinant expression vector containing the protein coding gene and a host cell. The protein is efficiently expressed through eukaryotic cells and engineering bacteria escherichia coli, and a fermentation and purification process suitable for an industrial scale is established in a matched manner. Functional experiments prove that compared with commercially available fibronectin products with a single structural domain, the double-structural domain recombinant human chemical fibronectin disclosed by the invention can remarkably promote proliferation, migration, adhesion and differentiation activity of human skin fibroblasts, and has wide application potential in the fields of skin repair, skincare and biomedical materials.

There is provided a viral vector having a lipid bilayer envelope comprising an antibody binding domain displayed on the exterior of the envelope that is cell-type specific; a viral envelope protein displayed on the exterior of the envelope that is able to facilitate infection of the same cell type; and a nucleic acid molecule comprising a promoter expressible in the same cell type. Further provided are methods of making the viral vector and methods of using the viral vector to modify cells and treat diseases / conditions.