83 results about "Humanized mouse" patented technology

The invention provides sgRNA and a gene vector for inhibiting bladder cancer by targeting human lncRNA-UCA1 and an application of the sgRNA; specifically, sgRNA sequences of an lncRNA-UCA1 gene and a PD-1 gene suitable for CRISPR-Cas9 targeted splicing are designed; by transforming plasmids of specific splicing lncRNA-UCA1 gene and CRISPR-Cas9 nuclease gene into human bladder cancer cells, the expression of the lncRNA-UCA1 gene drops so as to inhibit the growth of tumor cells; and the plasmid, together with a human PD-1 gene targeted knockout vector, is transformed into a humanized mouse model of bladder cancer transplanted tumor, so as to obviously inhibit the growth of tumors. According to the invention, the vector is simple in preparing steps, the sgRNA is good in targeting property and the CRISPR-Cas9 is high in knockout efficiency.

Provided are a B cell-derived iPS cell generated using a convenient technique, a technology for providing a human antibody at low cost using the iPS cell, an immunologically humanized mouse prepared using cells differentiated from the iPS cell, and the like. Also provided are a cloned cell obtained by contacting a B cell with nuclear reprogramming factors excluding C / EBPα and Pax5 expression inhibiting substances, particularly nucleic acids that encode Oct3 / 4, Sox2, Klf4 and c-Myc, wherein the cloned cell has an immunoglobulin gene rearranged therein and possesses pluripotency and replication competence (B-iPS cell). Still also provided are a method of producing a monoclonal antibody against a specified antigen, comprising recovering an antibody from a culture of B cells obtained by differentiating a B-iPS cell derived from a B cell immunized with the specified antigen, and a method of generating an immunologically humanized mouse, comprising transplanting to an immunodeficient mouse a human immunohematological system cell obtained by differentiating a B-iPS cell.

The invention belongs to technical field of animal genetic engineering, and specifically relates to immunodeficient mice, a manufacturing method thereof and applications. The manufacturing method comprises using NOD-Scid IL2rg- / - immunodeficient mice (NSI mice), and deleting Foxnl gene or Fah gene. Through deleting the Fah gene on the NSI mice, NSIF mice are obtained. The NSIF mice can be used to efficiently establish a novel humanized mouse model, used for liver physiological and pathological research. Through deleting the Foxnl gene on the NSI mice, the NSIF mice are obtained. The NSIF mice have no body hair, and immune system is further defected. The NSIF mice provide convenience for establishment, monitoring, and measurement of solid tumor.

The present invention relates to organoids derived from a single cell, such as a prostate cancer cell, and methods and compositions relating to the production and use thereof, including cell culture medium for producing organoids and methods of personalized treatment for prostate cancer. The invention further provides a humanized mouse comprising a prostate organoid derived from a patient's prostate cell.

The present invention relates to organoids derived from a single cell, such as a prostate cancer cell, and methods and compositions relating to the production and use thereof, including cell culture medium for producing organoids and methods of personalized treatment for prostate cancer. The invention further provides a humanized mouse comprising a prostate organoid derived from a patient's prostate cell.

The invention provides an ACE2 cell humanized mouse model as well as a construction method and application thereof. The mouse model adopts an immunodeficient mouse as a parent and the body of the mouse contains humanized cells for overexpressing an ACE2 receptor. The mouse model can overexpress the ACE2 receptor in human cells in the body of the immunodeficient mouse, the infection efficiency of acoronavirus taking the ACE2 receptor as an infection medium is improved, meanwhile, xenograft rejection can be avoided, and background pollution is reduced. In addition, the mouse model can also be used for transplantation and immune reconstruction of human immune cells, and is of great significance for further research on the killing effect of the human immune system on the virus, screening of vaccines and evaluation of immune treatment means.

The invention relates to a construction method and application of a humanized mouse model, in particular to a construction method and application of a transgenic mouse model of a human Nbs1<c.657del5> gene. The method includes: constructing a 5bp deletion mutation-containing BAC carrier in the human Nbs1 gene, conducting pronuclei microinjection, and performing screening to obtain 3 stable transgenic lines for high expression and low expression of the human Nbs1 gene. The transgenic mouse involved in the invention has the phenotypes of delayed puberty, uniform shortening of body length and bone dysplasia at certain proportion in one of the lines, and a new mouse model is established for Nijmegen breakage syndrome diseases. At the same time, as the Nbs1 gene function impairment is closely related to cancers, the transgenic model can be applied to short-term carcinogenic tests in drug pre-clinical safety evaluation, thus providing a potential substitution model for traditional biennium carcinogenic tests and also providing an effective tool for research of carcinogenesis mechanisms.

The present invention provides embryonic stem cells obtainable from an embryo of an immunodeficient mouse which is deficient in both Rag2 and Jak3 genes by culture in the presence of a GSK3 inhibitor and an MEK inhibitor, as well as a transgenic mouse, which is created with the use of these embryonic stem cells.

The invention discloses a humanized mouse. A mouse-human fusion CD47 gene is expressed on humanized cells of the humanized mouse and is shown in SEQ ID NO.1; an extracellular portion of the gene is a mouse CD47 sequence, and a transmembrane portion and an intracellular portion are human CD47 sequence; or the extracellular portion and the transmembrane portion are mouse CD47 amino acid sequences, and the intracellular portion is a human CD47 amino acid sequence. The humanized mouse has the humanized cells of the mouse-human fusion CD47 gene, extracellular information in an in-vivo environment of the mouse can be transmitted to the humanized cells and can be perceived by the humanized cells and the humanized cells have corresponding responses under the condition that the humanized cells are not swallowed by phagocytic cells, and the humanized cells in the humanized mouse grow and develop normally and play functions.

Belonging to the technical field of animal genetic engineering, the invention in particular relates to an immunodeciency mouse model, a preparation method and application thereof. The preparation method employs NOD-Scid IL2rg- / -immunodeficiency mouse (NSI mouse) to knock out Foxnl gene or Fah gene. According to the invention, an NSIF mouse is obtained by knockout of Fah gene from an NSI mouse, the NSI mouse can be used for efficient construction of a novel humanized mouse model, and can be used for physiological and pathological study of liver. In the invention, the NSIF mouse is obtained by knockout of Foxn1 gene from the NSI mouse, has no body hair, and the immune system has further defect, and the immunodeciency mouse model is easy for construction, monitoring and measurement of solid tumors.

The invention provides a method for preparing a TIM3 humanized animal mode based on a gene modification technology. The method comprises the following steps of: replacing an extracellular region and atransmembrane region coded by a mouse source Havcr2 gene with an extracellular region and a transmembrane region coded by a human source HAVCR2 gene on a mouse with a sound immune system; reserving an intracellular region of the mouse Havcr2 gene; and constructing a mouse model capable of interacting with an anti-human source TIM3 monoclonal antibody. Compared with common mice, the model realizesthe humanization transformation of key target molecules, retains the complete immune system, can be used for screening and evaluating drugs aiming at human genes, and is an ideal pre-clinical drug test model.

The invention described herein provides non-HLA matched humanized mouse model (e.g., NSG mouse model) with patient-derived xenograft (PDX), as well as methods of making and using the same.

CRISPR / Cas9-mediated genome editing holds clinical potential for treating genetic diseases, such as Duchenne muscular dystrophy (DMD), which is caused by mutations in the dystrophin gene. Here, usingthree promoters to drive expression of the same DMD guide RNA, a more robust and safe form of genome editing was achieved in a humanized mouse model for DMD with a deletion in exon 50, and in a DeltaEx50-MD Dog.

The invention provides a method for preparing a TIGIT humanized mouse model. According to the method, TIGIT extracellular regions and introns of gene sequences of extracellular regions of a mouse arepartially humanized, all sequences including introns and UTR in transmembrane regions and extracellular regions of the mouse are still mouse sources, and the internal regulatory sequences and completeintracellular signal transduction capacity of the genes are preserved in the manner; and by virtue of a humanized model constructed by the method, the original endogenous expression property of TIGITis realized, humanized regions (antibody combination regions) are maximized, the missing of an effective antibody is avoided, and the humanized model can be used for screening and evaluating drugs aiming at human TIGIT genes and is a very ideal preclinical drug testing model.

The invention relates to a chimeric antigen receptor, a lentiviral vector, a human dendritic cell, a cell line, an immunosuppressive solid tumor treatment drug, and a preparation method and application thereof, and belongs to the technical field of chimeric antigen receptors. The intracellular signal domain of the chimeric antigen receptor is selected from at least one of TLR4, TNFR2, Dectin-1 and Fc receptor gamma chain intracellular domain structures. In the presence of tumor targets, the chimeric antigen receptor disclosed by the invention can effectively activate human dendritic cells in vivo and in vitro, and can resist the environment formed by immunosuppressive molecules CTLA4-Ig and PD-L1, so that the ability of traditional CAR-T cells to remove immunosuppressive solid tumors is improved. According to the invention, in a clinically related humanized mouse tumor model, the human dendritic cell modified by the chimeric antigen receptor can effectively reverse an immunosuppressive tumor microenvironment and reactivate in-vivo depleted CAR-T cells, so that the progress of solid tumors is inhibited.

The invention relates to a preparation method of an NOD-genetic background neutropenic humanized mouse model, and belongs to the technical field of genetic engineering and genetic modification. The preparation method comprises the step of knocking out a Gfi1 gene from an NOD mouse to obtain the NOD-genetic background neutropenic humanized mouse model. The invention achieves specific knockout of the key gene Gfi1, which controls mouse neutrophil development, from the NOD-genetic background mouse model through a CRISPR / Cas9 system for the first time, and the novel NOD-genetic background neutropenic humanized mouse animal model is obtained. The mouse model has the potential of accepting heterotransplantation and provides a new concept for development of a brand-new humanized mouse.

The present invention provides for inhibition or blockade of immunomodulatory cell receptors to facilitate improved or complete reconstitution of a human immune system in laboratory animals, improve animal health, and improve animal longevity. Thus, the invention relates generally to compositions and methods of generating and using transgenic non-human animals that are engrafted with a human hematopoietic system involving anti-CCR5 agents. In various embodiments, the human hematopoietic system engrafted transgenic non-human animals of the invention are useful as systems for the in vivo evaluation of the growth and differentiation of hematopoietic and immune cells, immune responses, vaccines and vaccination regimens, and human pathogens and production and collection of immune mediators, including human antibodies.

This invention refers to a mouse for human hepatitis studies wherein the mouse has been injected with CD34+ stem cells and wherein the mouse is immunocompromised, as well as a method of manufacturing a mouse model comprising administering CD34+ stem cells as defined herein into an immunocompromised mouse as defined herein. The invention also refers to the use of a mouse as defined for testing the efficiency of putative anti-HBV or anti-HCV drugs or for characterizing changes in viral quasispecies during HBV or HCV infection.

The invention provides a transgenic vector, a method for rapidly constructing an ACE2 humanized animal model by using the transgenic vector, and application of the ACE2 humanized animal model by aiming at research and development of SARS-CoV-2 drugs. The transgenic vector comprises a PiggyBac transposon 5'end inverted repeat sequence (ITR), a CAG promoter, a human ACE2 coding region, a ribosome access site (IRES), firefly luciferase, a dial rat hepatitis post-transcriptional regulatory element (WPR), a polyA site and a 3 'end inverted repeat sequence (ITR), the transgenic vector can efficiently insert human ACE2 and luciferase gene expression cassettes into a mouse genome, and the luciferase and human ACE2 expressed transgenic mice can be rapidly screened through a luciferase living body imaging system.

The present disclosure provides, in part, a priming and boosting vector-based platform to develop vaccines against pathogensthat is tailored to elicit a broad T cell response targeting conserved viral epitopes. The universal vaccines are prepared against an immunogen of an infectious pathogenic organism selected from a virus, a bacteria, a fungus or a protozoan comprising at least one ribonucleic acid (RNA) polynucleotide comprising an open reading frame encoding at least one polypeptide antigen or an immunogenic fragment thereof, wherein the polypeptide antigen, or the immunogenic fragment thereof, comprises a conserved internal protein that is enriched in CD8+ T cell recognition antigens. The effectiveness of the priming and boosting platform is tested in a humanized mouse model comprising a fully functional human immune system.

Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR / Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.

The invention provides a humanized mouse tumor model. The humanized mouse tumor model is characterized by being obtained by transplanting human thymus tissues and CD34+ hematopoietic stem cells homologous with the thymus tissues. The humanized mouse tumor model transplanted by thymus and hematopoietic stem cells is constructed for the first time. The humanized mouse tumor model is determined to have a complete immunosuppression microenvironment, is suitable for overall evaluation of solid tumor immunotherapy, and can be applied to evaluation of feasibility and effectiveness of immunotherapy curative effects. The humanized mouse tumor model makes up for singleness and model incompleteness of existing tumor immunotherapy evaluation methods, and provides reference value for clinical research.Compared with traditional models, the humanized mouse tumor model supplements key effects of a human immune system in immunotherapy.

The invention discloses a humanized mouse universally suitable for left and right hands, which is not only suitable for the operation of right hands, but also meets the handedness requirement on left-handers without arranging the special mouse of the left-handers additionally and fully embodies people orientation. The humanized mouse at least comprises a mouse body, a preposed left key, a preposed right key, a roller wheel key and a control circuit internally arranged in the mouse body, wherein the preposed left key, the preposed right key and the roller wheel key are connected with the control circuit. The humanized mouse is characterized by also comprising an assistant left key, an assistant right key and an assistant roller wheel key which are arranged at the rear part of the mouse body and are matched with left hands to use; and the assistant left key, the assistant right key and the assistant roller wheel key are connected with the control circuit. On the basis of the structure of the prior and ordinary mouse, the all-purpose mouse suitable for the mouse hands according with the characteristic of the daily habits and customs of the left-handers is designed; and on the basis of not influencing the function of the right-hand operation, left-hand users realize the operation on computers through the same mouse. The humanized mouse has the advantages of novel and reasonable structure and easy operation.

A system and method configured to achieve hydrogel particle treatment for the reduction of metastatic burden in an immunocompetent syngeneic mouse model is described. The system seeks to achieve methodic optimization for the extraction and purification of extracellular vesicles (EVs) from cultured cells as well as from fresh breast cancer interstitium. Similarly, the system provides for lymph node remodeling by human breast cancer EVs in a humanized mouse model. Hydrogel particles are employed to convey cytokine releasing and EV-displaying treatment to afflicted bodies. The process and system is envisioned to be applied to other diseases and cancers, and is not therefore limited to metastatic cancers

The present invention provides for a recombinant nucleic acid molecule comprising a humanized mouse β-amyloid precursor protein (“APP”) gene comprising K670N, M671L and V717F mutations and uses thereof. The present invention further provides for a recombinant nucleic acid molecule comprising a region of a calcium-calmodulin dependent kinase IIα (“CaMKIIα”) promoter operatively linked to a β-amyloid precursor protein (“APP”) gene comprising at least one mutation and uses thereof.

Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR / Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.

The invention belongs to the fields of animal cell genetic engineering and gene genetic modification, and particularly relates to a construction method and application of an HER2 gene humanized mousetumor cell model. The method uses a CRISPR technology to knock out a mouse HER2 gene, and uses slow viral infection to insert a humanized HER2 gene into mouse breast cancer cell 4T1. The HER2 humanized mouse breast cancer humanized tumor model constructed by the method can be used not only for evaluation of antibody tumor drug efficacy, but also has important guiding significance for a clinical effect of drug development; and at the same time, the model is also an ideal model for safety evaluation of anti-human HER2 antibody drugs, pre-clinical in-vivo evaluation is performed on toxicology ofHER2 antibody drugs and HER 2-CAR T, HER 2-CAR NK immune cell therapy, and the market gap is filled.

The invention discloses a construction method of a CD73 humanized mouse model. The CD73 humanized mouse model is efficiently and successfully obtained by optimizing a targeting carrier and sgRNA usedin model preparation and verification steps. The model has remarkable advantages in screening application of CD73 targeted drugs and other immune checkpoints or small molecule drug combination.