81 results about "Humanized mouse" patented technology

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 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 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.

An embryonic stem cell that is obtained by culturing a mouse embryo, in which the whole or a part of domains of H2-D molecule of mouse MHC class I are substituted by domains of HLA-A molecule of humanMHC class I, in the presence of a GSK3 inhibitor and an MEK inhibitor; and a mouse that is produced using the embryonic stem cell.

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.

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.

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.

The invention uses a BAC (bacterial artificial chromosome) transgenic technique on BALB / c background to insert humanized CD3E and its complete regulation sequence into mouse genome and establishes a hCD3E transgenic mouse model which is applicable to screening drugs for colorectal cancer, hepatic cancer, melanoma, breast cancer, renal cancer and lymphoma; the range of bispecific antibody screeningtypes is greatly widened. The steps are optimized; the preparation success rate of the hCD3E transgenic mouse model is greatly increased; stably genetic mouse line is successfully attained at present. The mouse line allows co-expression of humanized CD3E(hCD3E) and murine CD3e(mCD3e); the CD3E humanized mouse has complete immune system; data are provided for the research and development of CD3E-TCB clinical drugs at home and aboard; the market blank is filled.

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.