192 results about "Mice transgenic" patented technology

A new method to capture, purify and expand antigen-specific T lymphocytes has been developed using magnetic beads coated with recombinant MHC class I molecules. This method was optimized using homogenous populations of naive T cells purified from mice transgenic for the 2C T cell receptor (TCR). These T cells were captured on beads coated with MHC class I molecules and the relevant antigenic peptides. MHC and peptide specificity was confirmed by the usage of irrelevant MHC peptide combinations. An enrichment of 800 to 1600 fold was measured, using 2C T cells mixed with irrelevant T cells, starting from a 2C T cell frequency of 1/3000. The same approach was used to purify antigen-specific CD8⁺ T cells from total CD8⁺ T cells from naive mice. The recovered cells could be expanded and specifically kill target cells in vitro; they had a significant effect in vivo as well. We expect this procedure to be suitable to purify and expand in vitro tumor- and virus-specific killer T cells for use in cell therapy.

Immunization of human antibody-producing transgenic mice, which have been created using genetic engineering techniques, with AILIM molecule as an antigen resulted in various human monoclonal antibodies capable of binding to AILIM and capable of controlling a variety of biological reactions (for example, cell proliferation, cytokine production, immune cytolysis, cell death, induction of ADCC, etc.) associated with AILIM-mediated costimulatory signal (secondary signal) transduction. Furthermore, it has been revealed that the human monoclonal antibody is effective to treat and prevent various diseases associated with AILIM-mediated costimulatory signal transduction, being capable of inhibiting the onset and/or advancement of the diseases.

The present invention is related to the identification of cancer stem cells using the MMTV-Wnt-1 transgenic mouse model. These cancer stem cells have a gene expression signature that allows them to be distinguished from their non-tumorigenic counterparts. Moreover, the gene expression pattern can also predict survival in a diverse group of solid tumors.

The invention discloses a gRNA sequence. The sequence is capable of editing a DNA sequence in the manner of taking a hepatitis B viral genome specific locus as a target sequence. The invention also discloses a CRISPR-SaCas9 system containing the gRNA sequence and a recombinant adeno-associated virus packaged with the system. The system and the packaging virus show higher HBV scavenging activity in cells and in transgenic mice body. On the 38th day after twice continuous high dose injection, the contents of HBsAg and HBeAg in experimental group mice serum, compared with the control group, are respectively reduced by 62.96+/-7.59% and 65.18+/-3.08%; the HBV DNA content in the serum, compared with the control group, is reduced by 92.82+/-3.67%; the liver and other visceral organs of the experimental mice are all free from any pathologic change, the off-target effect is also not detected and the application prospects of the gRNA sequence and the corresponding CRISPR-SaCas9 system provided by the invention in preparing the hepatitis B therapeutics are shown.

The construction of transgenic animal models of human Alzheimer's disease, and methods of using the models to screen potential Alzhe## disease therapeutics, are described. The models are characterized by pathologies similar to pathologies observed in Alzheimer's disease, based on expression of all three forms of the β-amyloid precursor protein (APP), APP695, APP751, and APP770, as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, predicted mutations in the APP gene, and truncated forms of APP that contain the Aβ region. Animal cells can be isolated from the transgenic animals or prepared using the same constructs with standard techniques such as lipofection or electroporation. The transgenic animals, or animal cells, are used to screen for compounds altering the pathological course of Alzheimer's disease as measured by their effect on the amount of APP, β-amyloid peptide, and numerous other Alzheimer's disease markers in the animals, the neuropathology of the animals, as well as by behavioral alterations in the animals.

The present invention relates to the discovery, identification and characterization of nucleotides that encode novel substrate-targeting subunits of ubiquitin ligases. The invention encompasses nucleotides encoding novel substrate-targeting subunits of ubiquitin ligases: FBP1, FBP2, FBP3, FBP4, FBP5, FBP6, FBP7, FBP8, FBP9, FBP10, FBP11, FBP12, FBP13, FBP14, FBP15, FBP16, FBP17, FBP18, FBP19, FBP20, FBP21, FBP22, FBP23, FBP24, and FBP25, transgenic mice, knock-out mice, host cell expression systems and proteins encoded by the nucleotides of the present invention. The present invention relates to screening assays that use the novel substrate-targeting subunits to identify potential therapeutic agents such as small molecules, compounds or derivatives and analogues of the novel ubiquitin ligases which modulate activity of the novel ubiquitin ligases for the treatment of proliferative and differentiative disorders, such as cancer, major opportunistic infections, immune disorders, certain cardiovascular diseases, and inflammatory disorders. The invention further encompasses therapeutic protocols and pharmaceutical compositions designed to target ubiquitin ligases and their substrates for the treatment of proliferative disorders.

An objective of the present invention is to provide a safe and effective vaccine therapy for Alzheimer's disease. A minus strand RNA viral vector carrying amyloid gene was constructed, and administered intranasally to 24- to 25-months-old APP transgenic mice. The level of serum anti-A 42 antibody was determined and showed to be markedly higher than the control. The results of histological investigation showed that the administration of a vector of the present invention markedly reduced senile plaques in all of the frontal lobe, parietal lobe, and hippocampus. The brain A level was also markedly reduced. Furthermore, the administration of a vector of the present invention did not result in lymphocyte infiltration in the central nervous system.

Provided are methods of treating and/or preventing dermatological disorders. Provided are methods of reducing skin inflammation, reducing pain, and/or reducing itch in a subject in need thereof. The methods may include administering to the subject an effective amount of a TRPV4 inhibitor. Further provided are compositions including a TRPV4 inhibitor compound in combination with a carrier, vehicle, or diluent that is suitable for topical application. Further provided is a transgenic mouse whose genome includes deletions of the Trpv4 gene in keratinocytes of the epidermis, wherein said transgenic mouse is a knockout for the Trpv4 gene in keratinocytes of the epidermis following keratinocyte-specific activation and expression of a site-specific recombination enzyme.

The invention provides a new reproducible transgenic mouse model for the study of tumor metastasis. In particular, the invention concerns the study of tumor metastasis in a NOD/SCID/γ_c^null transgenic mouse model.

We identified regions of the HIV-1 proteome with high conservation, and low variant incidence. Such highly conserved sequences have direct relevance to the development of new-generation vaccines and diagnostic applications. The immune relevance of these sequences was assessed by their correlation to previously reported human T-cell epitopes and to recently identified human HIV-1 T-cell epitopes (identified using HLA transgenic mice). We identified (a) sequences specific to HIV-1 with no shared identity to other viruses and organisms, and (b) sequences that are specific to primate lentivirus group, with multiclade HIV-1 conservation.

The invention provides novel coronavirus SARS-CoV-2mRNA vaccines and a preparation method and application thereof. The invention provides three mRNA vaccines, namely RBD, S1 and S vaccines. The RBD vaccine disclosed by the invention can induce a high-titer antigen-specific IgG antibody and a virus neutralization antibody after immunization with one dose, the high-titer neutralization antibody can be maintained for at least 26 weeks, and remarkable immune protection can be provided for human ACE2 transgenic mice in serum adoptive transfer protection experiments. The RBD and S vaccine disclosed by the invention can induce immune protection capable of completely resisting SARS-CoV-2 virus infection in the human ACE2 transgenic mice after immunization with two doses. A large number of experimental results show that the mRNA vaccine provided by the invention has good immunogenicity, forms powerful immune protection after immunizing an organism, and has a huge development potential.

The present invention relates to a novel animal model for amyloidopathies, especially Alzheimer' disease overexpressing human BACE and human APP London. This novel animal model exhibits several aspects of amyloidopathy and has utility in developping specific and general therapies for amyloidopathies. Moreover, this animal model can be used for screening methods to identify novel anti-amyloidogenic compounds and for testing their therapeutic effect. The present invention also relates to a method for producing the said double transgenic animals, to cells and cell lines derived from these animals and to a kit comprising these cells for screening compounds useful of amyloidopathies. Moreover, a method for the evaluation of the in vivo effects of beta-secretase activity on A-beta peptide generation, amyloidosis, neurodegeneration and AD pathology in these animals is provided.

The invention discloses HLA-A2 restrictive epitope polypeptide of an LMP2A protein source, which is polypeptide LMP2A264 and comprises 9 amino acids in the positions of 264 to 272; the sequence is QLSPLLGAV. Mycobacteria heat shock protein 70 (HSP70) is expressed, identified and purified; a transgene animal model for evaluating EBV relevant polypeptide vaccine in vivo tests is established; the immune research on inducing EBV specific CTL inside and outside healthy volunteers and transgene rats for the new EBV epitope polypeptide LMP2A264 is systemically researched and the tumor prevention andthe tumor treating test of the polypeptide LMP2A264 on LMP2A positive solid tumors are evaluated, thereby proving that the polypeptide LMP2A264 can induce LMP2A specific cell toxic T lymphocyte reaction. Therefore, the polypeptide LMP2A264 can be applied to prepare medicaments for treating or preventing LMP2A positive solid tumors.

The present invention relates to immunoglobulin anamorphosis and uses thereof. The invenion provides a humanied and embeded aiti-CD20 body used for treating positive malignant tumor and auto-immune disease.

The invention provides a construction method and an application of an HBeAg transgenic mouse model. The method comprises the following steps: CRISPR/Cas9 technology is adopted, an HBeAg gene is inserted into a pliver-HBeAg expression cassette at the Rosa26 gene locus in a fixed-point manner through homologous recombination, and a recombinant R26-e(Alb-HBeAg)1 targeting vector is constructed with an In-Fusion cloning method and contains a 3.3kb 5' homologous arm, pliver-HBeAg and a 3.3kb 3' homologous arm; Cas9mRNA, gRNA and the recombinant R26-e(Alb-HBeAg)1 targeting vector are micro-injectedinto a zygote of a C57BL/6J mouse, then the zygote is transplanted into the uterus of a C57BL/6J female mouse, and an HBeAg transgenic mouse is obtained through propagation and purification step by step. The transgenic mouse can specifically express HBeAg in liver, thereby being capable of applying to experimental animal models for researching HBeAg infection mechanism and evaluating treatment effects of therapeutic drugs and vaccines for chronic hepatitis B.

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 describes a dissociated cell culture system comprising cells of the hippocampus, one of the brain areas affected by Alzheimer's Disease (AD) or amyloid beta-related diseases. This culture system comprises hippocampal neuronal and glial cells from animal models of AD, particularly, but not limited to, double transgenic mice expressing both the human APP mutation (K670N:M671L) (mAPP), and the human PS1 mutation (M146L) (mPS1), and serves as a powerful tool for the screening and testing of compounds and substances, e.g., drugs, for their ability to affect, treat, or prevent AD or β-amyloid-related diseases. The effects of a test substance on the cells in this culture system can be quantitatively assessed to determine if the test substance affects the cells biochemically and/or electrophysiologically, and/or optically, and/or immunocytochemically. The present in vitro culture system is advantageous for AD drug screening, because it is rapid and efficient. By contrast, even in the fastest animal model of AD, pathology does not start before the end of the second month. If such in vivo animal models are used, it is necessary to wait at least the two month time duration or longer to test for drug efficacy for AD treatment or prevention. At the same time the present invention provides a tool for production of amyloid-beta that can be used for electrophysiological, behavioral, and toxicological studies.

The invention discloses a method for constructing an anti-mammitis transgenic mouse model and a special vector for the method. An anti-mammitis-related protein composition comprises lysostaphin and peptidoglycan endolysin B30; the peptidoglycan endolysin B30 derives from a Streptococcus agalactiae phage B30, and an amino acid sequence of the peptidoglycan endolysin B30 is sequence 2 in a sequence table; and an amino acid sequence of the lysostaphin is sequence 3 in the sequence table. The experiment proves that a transgenic plasmid for mammary gland-specific expression of the lysostaphin and the peptidoglycan endolysin B30 is constructed by using a mammary gland-specific expression vector; and the anti-mammitis transgenic mouse model is constructed by a microinjection method, a transgenic mouse with an anti-bovine mastitis gene is obtained, and a technical model is provided for further producing anti-mammitis transgenic calves.