1424results about "Viruses" patented technology

The invention relates to a nano antibody targeting cadherin 17 and application thereof, and relates to the technical field of immunology and molecular biology, the amino acid sequence of a complementary determining region of the nano antibody targeting cadherin 17 comprises CDR1 shown as any one of SEQ ID NO: 21-32, CDR2 shown as any one of SEQ ID NO: 34-45, and CDR3 shown as any one of SEQ ID NO: 47-58. According to the invention, an alpaca immune phage display library is constructed, a series of nano antibody molecules targeting cadherin 17 (CDH17) are screened from the alpaca immune phage display library, and functions and applications of the nano antibody are verified at various levels of CDH17 antigen protein, CDH17 target cells, CDH17 CAR-T cells and the like.

The invention relates to a humanized nano antibody targeting cadherin 17 and application of the humanized nano antibody, and relates to the technical field of immunology and molecular biology. The complementarity determining region of the humanized nano antibody comprises a CDR1 of which the amino acid sequence is shown as SEQ ID NO: 2, a CDR2 of which the amino acid sequence is shown as SEQ ID NO: 4 and a CDR3 of which the amino acid sequence is shown as SEQ ID NO: 6; a framework region of the humanized nano antibody comprises an FR1 of which the amino acid sequence is shown as any one of SEQ ID NO: 1 and SEQ ID NO: 8, an FR2 of which the amino acid sequence is shown as any one of SEQ ID NO: 3, SEQ ID NO: 9 and SEQ ID NO: 11, an FR3 of which the amino acid sequence is shown as any one of SEQ ID NO: 5 and SEQ ID NO: 10, and an FR4 of which the amino acid sequence is shown as SEQ ID NO: 7. According to the humanized nano-antibody, the immunogenicity of the nano-antibody is reduced, the targeted binding activity and killing activity are improved, and the humanized nano-antibody can be used for developing immunodetection reagents, CAR-T / NK cell drugs and antibody drugs.

The present invention relates to T lymphocytes targeting CLD18A2 and a preparation method and application thereof. The inventors have successfully found a target gene CLD18A2 suitable for developing CAR T cells from a number of tumor-related genes for the first time, and successfully prepared CAR T cells targeting CLD18A2, thereby providing a new treatment method for pancreatic cancer, gastric cancer and other tumors.

The present invention relates to the field of genetic engineering. Specifically, the present invention relates to cytosine deaminase and use thereof in base editing. More specifically, the present invention relates to a base editing system based on a newly identified cytosine deaminase, a method for base editing a target sequence in the genome of an organism (e.g., a plant) using the base editing system, and a genetically modified organism (e.g., a plant) produced by the method and progenies thereof.

The present invention relates to methods and compositions for reducing the immunogenicity of chimeric Notch receptors, and specifically to transcription factors useful for controlling gene expression delivered to tissues by such chimeric Notch receptors.

The invention relates to the technical field of antibodies, in particular to a Trop2 combined nano antibody, a chimeric antigen receptor and application of the Trop2 combined nano antibody and the chimeric antigen receptor. The Trop2-binding nano antibody provided by the invention can efficiently and specifically recognize and bind Trop2 protein, and can be used for diagnosing and treating diseases taking Trop2 molecules as markers. The invention further provides CAR and CAR-T cells which are combined with the Trop2 protein, and the CAR-T cells have a good Trop2-targeting immune clearance effect, can be used for specifically recognizing and killing cells expressing Trop2, can be used for improving and treating diseases with Trop2 molecules as markers and have a good application prospect in tumor diagnosis and treatment.

The invention relates to the field of gene engineering. In particular, the present invention relates to cytosine deaminases and their use in base editing. More specifically, the invention relates to a method for screening and identifying a deaminase, a base editing system based on a newly identified cytosine deaminase, a method for editing a target sequence in a genome of an organism (such as a plant) by using the base editing system, and a method for screening and identifying the target sequence. As well as genetically modified organisms (e.g., plants) and progeny thereof produced by the method.

The invention relates to the technical field of medicine screening, in particular to an active substance screening platform and application thereof. The active substance screening platform comprises a cell combination; the cell combination comprises immunoregulation screening cells and antioxidant screening cells; the immunoregulation screening cell is a mouse mononuclear macrophage RAW 264.7 carrying an NF-kappa B element conserved sequence and a reporter gene; the antioxidant screening cell is a porcine small intestine epithelial cell IPEC-J2 cell carrying an ARE element conserved sequence and a reporter gene. The invention provides a screening platform based on a specific cell combination, which can quickly obtain an active substance with immune regulation, antioxidation or two functions from a large number of candidate active substances, has the advantages of low cost and high efficiency, and has important application value.

The present application relates to systems and methods to generate B cells genetically modified to express selected antibodies. The systems and methods can be used to: eliminate the need for classical vaccination; providing protection against infections available for current vaccination; providing protection against infections when the patient is additionally subjected to immunosuppression; and / or provides benefits provided by therapeutic antibodies, such as in the treatment of autoimmune disorders.

Compositions, methods and systems for targeted delivery using one or more shuttles operably linked to one or more cargos (e.g., cargo polypeptides, e.g., cargo oligonucleotides) and subsequent quantification of an abundance of one or more cargos (e.g, proteins) in a mixture (e.g., a complex mixture (e.g., in vivo)) or in a specific cell, tissue, or organ of interest (e.g., in vivo) using barcodes (e.g., peptide barcodes), binders (e.g., polypeptide binders), and binding agents (e.g., phage) are provided herein.

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

The present disclosure provides drug-responsive domains derived from human carbonic anhydrase 2 that can modulate the protein stability of human interleukin-15 (IL15) payloads, as well as compositions and methods of use thereof.

The invention relates to the technical field of tumor immunotherapy, in particular to a dual-targeting chimeric antigen receptor, a recombinant expression vector, an anti-tumor natural killer cell and application, and provides a PD1-DAP10-41BB-P2A-NKG2D-Ig4-CD28-41BB-CD3 zeta fusion receptor.The dual-targeting chimeric antigen receptor can target PD-L1 on the surface of a tumor cell, can also recognize NKG2DLs and can be used for preparing anti-tumor natural killer cells. The broad spectrum of the NK cells is greatly improved, and meanwhile, the immune escape of tumor cells is also reduced.

A non-integrating viral delivery system is disclosed. The system includes a viral carrier, wherein the viral carrier contains a defective integrase gene; a heterologous viral episomal origin of replication; a sequence encoding at least one initiator protein specific for the heterologous viral episomal origin of replication, wherein expression of the sequence encoding the at least one initiator protein specific for the heterologous viral episomal origin of DNA replication is inducible; and at least one gene, gene product, shRNA, siRNA, miRNA, or other RNA of interest.

Provided herein are cell surface receptors that include an extracellular binding domain, a transmembrane domain, an intracellular signaling domain, and a protease cleavage site disposed between the extracellular binding domain and the intracellular signaling domain. In certain aspects, the cell surface receptors are engineered cell surface receptors, such as chimeric antigen receptors (CARs). Also provided are cells that include such receptors (e.g., where the cells express the receptors on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the cell surface receptors, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for regulating signaling of a cell surface receptor, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable cell-based therapy to an individual.

The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and / or NK cells. The methods can include inhibitory RNA molecule(s) and / or engineered signaling polypeptides that can include a lymphoproliferative element, and / or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and / or genetically modified T cells and / or NK cells are provided, such as, for example, those including riboswitches, MRB-CARs, recognition domains, and / or pH-modulating agents.

The invention discloses an IL10-secreting and BAFFR-targeting chimeric antigen receptor, a CAR-T cell and application. The IL10-secreting and BAFFR-targeting chimeric antigen receptor comprises a signal peptide region, a BAFFR-targeting antigen binding domain, a hinge region, a transmembrane structural domain, a co-stimulation structural domain, a signal transduction structural domain and human IL10 which are sequentially connected from an amino terminal to a carboxyl terminal, wherein the signal peptide region, the BAFFR-targeting antigen binding domain, the hinge region, the transmembrane structural domain, the co-stimulation structural domain, the signal transduction structural domain and the human IL10 are sequentially connected from the amino terminal to the carboxyl terminal; the co-stimulation structural domain comprises a CD28 co-stimulation structural domain and a 4-1BB co-stimulation structural domain which are connected, and the signal transduction structural domain is ITAM1 of CD3 zeta. The kit can specifically aim at autoimmune B cells, and immunodeficiency and patient infection caused by full B cell deletion are avoided. The secretion of IL10 on the CAR-T cells can reduce the depletion rate of the CAR-T cells in vivo, so that the long-acting inhibition effect on the disease process is achieved.

Disclosed is a novel classification of conjugate virus-like particles (VLPs). These conjugate VLPs conjugate to a wide variety of tumors and contain epitopes that are recognized by past T-cell responses already present in the host's body. These epitopes originate from pathogens or past vaccinations (such as early childhood vaccines). This triggers pre-existing cytotoxic immunity in the body acquired through past infection or past childhood vaccination, which is redirected to tumor cells for tire elimination of cancer and forms long-term anti-tumor immunity. The described conjugate VLPs are useful in adapting a wide range of tumors to responses from existing immunity, bypassing the need to identify tumor antigens or generate tumor-specific immune responses. Importantly, the compositions and methods described herein expand opportunities for treating affected cancer types in subjects with a history of cancer that could not be targeted due to various technical and biological limitations of currently available immunotherapeutic agents.

The present disclosure relates to the field of molecular virology, in particular to nucleic acid molecules encoding viral genomes and self-replicating RNA (srRNA) constructs of modified equine encephalitis viruses, pharmaceutical compositions containing same, and the use of such nucleic acid molecules and compositions for the production of desired products in cell culture or in an organism. Also provided are methods for eliciting an immune response in a subject in need thereof, and methods for preventing and / or treating cancer.

Provided are cell models of eye diseases, methods and compositions for treating eye diseases.

Disclosed herein are an engineered immune cell with CIITA gene knock-out and use thereof. According to the present invention, an sgRNA specifically targeting CIITA gene is designed and synthesized, which can accurately target CIITA gene to achieve gene knock-out with high knockout efficiency. The provided sgRNA can be used for preparing a universal CAR-T cell.

The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and / or NK cells, in shorter times than previously and / or in whole blood or a component thereof. In some embodiments a lymphodepletion filter assembly is used before or after forming a reaction mixture where lymphocytes are contacted with recombinant retroviral particles in a closed system, to genetically modify the lymphocytes.

The present inventions provide covalently surface modified adeno-associated viruses can comprise gene of interest (GOIs) and advantageously can be targeted to certain cell and tissue types for preventative and therapeutic purposes. The present inventions further provide systems and methods for engineering adeno-associated virus (AAV) to create covalently surface modified adeno-associated viruses, and methods of purifying such covalently surface modified adeno-associated viruses. The inventions further include covalently surface modified adeno-associated viruses and preparations and products comprising such covalently surface modified adeno- associated viruses.

The present invention finds the effect of ATXN2 and / or ATXN2L in circadian rhythm. Thus, the present invention provides methods, medicaments and uses for modulating circadian rhythm in a subject. Meanwhile, the invention further provides a method for detecting the circadian rhythm of a subject and a biomarker capable of indicating circadian rhythm abnormity. The invention provides a brand new way and means for adjusting the circadian rhythm.

The invention provides a method for rejuvenating cells by reprogramming in a phase-free separation transcription factor mediated initiation stage. Through improvement of phase-free separation of transcription factors, a recombinant vector is constructed and introduced into a target cell, and the cell is controlled in a reprogramming starting stage, so that the technical effect of rejuvenation is achieved.

The invention provides improved compositions for adoptive T cell therapies for B cell related conditions.

The invention provides a glycosyl-modified fusion protein, a nucleic acid molecule, an expression vector, a host cell and application. In the first aspect, the invention provides a glycosyl-modified fusion protein which comprises a mouse Fc variant and a prostatic cancer tumor antigen, the mouse Fc variant is obtained by performing amino acid mutation and non-mammalian glycosylation modification on a mouse Fc fragment; the mouse Fc variant comprises at least one of alanine at the 223 site, alanine at the 228 site, alanine at the 230 site, leucine at the 330 site and glutamic acid at the 332 site; the non-mammalian glycosylation modification does not comprise sialic acid modification; the site numbering is carried out according to an EU numbering system; the mouse Fc variant improves combination of a mouse Fc fragment and DC cells and DC activation, including proliferation and activation of specific T cells.

The present invention relates to a method for making a non-human primate model of cerebral infarction comprising a step of administering endothelin to the brain basal nucleus-thalamic region of a non-human primate, thereby inducing brain basal nucleus disorders, thalamic disorders and endocystic disorders, and a method for treating subacute stages-containing NeuroD1 protein or a polynucleotide encoding a NeuroD1 protein The pharmaceutical composition can be used for treating chronic cerebral infarction, transbronchial infarction or cerebral infarction with brain disorder in a transbronchial dominating region.

Provided herein are methods of ex vivo administration of a lipid particle or a payload gene, to a subject. In some embodiments, the methods are in-line methods of administration of a lipid particle or payload gene that are performed in a closed fluid circuit. Also provided are related compositions, containers, and systems in connection with the provided methods.

The invention provides improved compositions for adoptive T cell therapies for B cell related conditions.