53 results about "Rhesus macaque" patented technology

The present invention relates to novel p75 heterodimer specific anti-human IL-12 antibodies that are characterized by a higher potency and greater efficacy in neutralizing human IL-12 bioactivity than known heterodimer specific IL-12 monoclonal antibodies. The heterodimer specific antibodies recognize one or more epitopes of the human IL-12 p75 heterodimer, but do not bind to the p40 subunit alone. The heterodimer specific IL-12 antibodies neutralize rhesus monkey IL-12 bioactivity with a potency similar to their potency for neutralizing human IL-12 bioactivity making them useful IL-12 antagonists for in vivo studies in the rhesus monkey.

The invention discloses a nano vaccine taking an SARS-CoV-2 virus S protein RBD region as an antigen and a preparation method of the nano vaccine. An expression vector with an SARS-CoV-2 virus S protein RBD region gene sequence is transfected into 293T, 293i and CHO cell lines for antibody expression, and the required vaccine is obtained after protein extraction, ultrafiltration enrichment, antibody affinity chromatography purification, protein collection after purification, PBS dialysis and aluminum hydroxide adjuvant mixed incubation. The vaccine is a protein for expressing an amino acid sequence of the SARS-CoV-2 virus S protein RBD region, 24 monomers in a cell can be self-assembled into a sphere structure, and an SARS-CoV-2 virus S protein RBD peptide fragment subjected to fusion expression is displayed on the surface of a sphere. The vaccine has high neutralizing activity on the SARS-CoV-2 virus, and can effectively inhibit infection of the virus on vero cells. A toxicity attacking experiment shows that the vaccine can obviously and effectively protect the infection and damage of the SARS-CoV-2 to rhesus monkeys, and an excellent candidate vaccine is provided for the prevention and control of the current COVID-19 epidemic situation.

The invention relates to a method for establishing an artery ischemia model of a brain of a rhesus monkey and an evaluation method. The constructing method adopts the mode of directly puncturing femoral arteries of an experimental monkey to perform the intravascular interventional operation under the direct view of a digital subtraction angiography, and establishes the chronic cerebral infarctionprimate model by using a micro-catheter to block the arteries in the brain of the experimental monkey and controlling ischemia time. The model is a quite reasonable cerebral ischemia-reperfusion animal model, and the pathological characteristics of the monkey cerebral injury model established by the method are similar to clinical manifestation; and moreover, the model is stable and reliable and issuitable for all kinds of curing therapeutic research and related basic research.

The invention relates to a method for preparing an animal model of an insulin-dependent diabetes. In the method, the pancreas part of a primate is excised and a method of streptozotocin induction is used together to establish a rhesus monkey diabetes model, wherein the using method and the dosage of streptozotocin are as follows: the streptozotocin is injected in vein in a ratio of 15 to 20 mg / kgeach time. The method establishes the rhesus monkey diabetes model by combining the excision of the pancreas with the method of streptozotocin (STZ) induction, and carries out observation and comparison of physical indexes of the model. The insulin treatment scheme is economical, safe and feasible.

The invention discloses a method for preparing an animal pulmonary fibrosis model. According to the method, bleomycin is applied to a primate, the application dose of the bleomycin is 7 mg / Kg for each time, and application is performed once for each week and totally performed twice. The invention further provides a rhesus monkey pulmonary fibrosis model prepared with the method and an application of the rhesus monkey pulmonary fibrosis model. The rhesus monkey pulmonary fibrosis model is established successfully, an operation process is simple and easy to repeat, and the model can be used for new biotechnological drug evaluation which cannot be finished by a rodent model and has bright clinical application prospects.

The invention discloses a method and purpose for constructing a TCM spleen deficiency syndrome AIDS monkey model. Among existing AIDS experimental animals, a monkey resembles to mankind the most. The inventor successfully constructs an HIV infected rhesus monkey TCM spleen deficiency syndrome composite model by two methods respectively. The first method is to carry out gavage with raw rhubarb concentrate to a create spleen deficiency syndrome and then carry out intravenous injection of infected SIV viruses. The second method is to carry out gavage with raw rhubarb concentrate to create the spleen deficiency syndrome after rhesus monkeys is infected with SIV viruses through intravenous injection. Based on the understanding of infection course, pathogenic processes and pathological changes of AIDS viruses in a spleen deficiency syndrome model, research on attack of infected target organs, target tissue and target cells to the immune system, on response of cells of the immune system, on the evolution law of a TCM syndrome, etc., is carried out. The established TCM spleen deficiency syndrome HIV infected monkey composite model in the invention plays an irreplaceable role in studying TCM pathogenesis and evolution of symptomatology of TCM for AIDS and in evaluating drug effects of anti-AIDS TCMs and compounds.

The present invention provides a breast cancer resistance polynucleotide and protein of Macaca mulata (rhesus monkey) and uses thereof. The present invention also provides anti-BCRP antibodies and uses thereof, particularly as a hematopoietic stem cell marker.

The invention provides a gene, which is a deoxyribonucleic acid (DNA) molecule with the sequence of nucleotide illustrated as the SEQ ID NO:1. A fusion protein of the gene code and a preparation method and application thereof are further provided. The fusion protein mm CTLA4Ig can prevent a CD 28 molecule from being combined with a B7 molecule, further suppresses activation of a T cell, has an obvious immunosuppression function, can be used for preparing an immunosuppressive agent, and is particularly suitable for the immunosuppressive agent for rhesus monkeys.

The invention discloses a method for establishing a Macaca fascicularis experimental autoimmune encephalomyelitis model and application thereof. According to a concrete technical scheme in the invention, the method comprises the following steps: preparing an emulsion (an MOG solution: CFA = 1: 1) from MOG 34-56 (100 mu g / ml); narcotizing Macaca fascicularis for experiments and injecting 1 ml of the prepared emulsion at 10 injection points; carrying out immunization injection of the emulsion (secondary immunization) according to the above-mentioned method and dose in 7 days after the primary immunization injection (primary immunization); carrying out clinical observation in one day after primary immunization and recording clinical scores; and determining pathogenic sites, degrees and the like by using an MRI iconographic method at pathogenic time nodes. The model established in the invention has an application value which cannot be achieved by other rodent models, has the characteristics of recurrence-alleviation type attacks, low cost, wide availability of Macaca fascicularis for experiments and the like compared with a Macaca rhesus model and has a wide application scope in fields related to multiple sclerosis diseases.

The invention discloses an exclusive method for detecting the content of iohexol in plasma of rhesus monkeys and application thereof to evaluation of the influence of a drug on GFR (Glomerular Filtration Rate), and belongs to the field of drug evaluation. The exclusive method comprises the following steps: (1) standard product working solution and standard curve preparation: preparing standard production working solutions in various concentrations; (2) preparation of an internal standard production solution preparing an iohexol impurity I working solution; (3) sample pretreatment; (4) determination of iodexol: determining under the conditions that a C18 is used as a chromatography column, a mobile phase comprises a mobile phase A which is methanol and a mobile phase B which is phosphoric acid water, isocratic elution with elution time of 10 minutes , 20 to 40 DEG C in temperature and 0.2 to 1.5 mL / min in flowing speed, the detection wavelength of a chromatogram is 190 to 320 nm and thesampling volume is 1 to 20 mu L. The exclusive method disclosed by the invention is capable of detecting the content of the iohexol, is accurate and simple and is time-saving and labor-saving; the dosage of the iohexol required for determining and evaluating the GFR by utilizing the iodexol clearance rate is smaller, and the safety of kidney is greatly improved; the exclusive method is simple andreliable, the exclusiveness is strong, and effective experimental data can be provided for clinical application.

The present invention relates to PEG modified anti-HIV polypeptides. Specifically, cysteine is added to the N terminal, the C terminal or the 10th position of the C34 polypeptide, a polyethylene glycol group with maleic amide modification is coupled to the cysteine through Michael addition reaction, PEGylation modification is performed on the C34 polypeptide, the molecular weight of a PEG part is10000 or above, preferably 10000 to 100000 DEG C, and more preferably 10000 to 50000 DEG C. The modified C34 peptide has obviously increased water solubility and rat plasma half-life period, is easierto enter lymph nodes and has stronger anti-HIV virus activity on rhesus monkeys which are acutely infected with SHIVSF162P3. The invention also relates to a preparation method and application of thePEG modified anti-HIV polypeptide.

The invention discloses application of virus macrophage inflammatory protein vMIP-II for inducing dephosphorylation of CD8<+> T cells to form Tcm. The vMIP-II for inducing dephosphorylation of the CD8<+> T cells to form the Tcm is developed in a laboratory and is verified by the National Institute for Control of Pharmaceutical and Biological Products. According to the invention, the CD8<+> T cellsare researched through a rhesus SIV infection model. The research finds that: the vMIP-II can enable Tcm to be proliferated depending on the dosage of the vMIP-II, and the differential gene of the proliferative cell is mainly enriched in a chemokine receptor and a phosphorylation pathway. The research further finds that: the proliferation is as follows: the vMIP-II closes a CD8<+> T chemokine receptor, promotes low expression of G protein, reduces the concentration of intracellular Ca<2+> and mitochondrial membrane potential, inhibits phosphorylation related genes, and promotes low expressionof phosphorylated proteins ERK1 / 2 and Akt, so that a CD8<+> T phosphorylation signal is weakened, metabolic reprogramming is carried out, and the CD8<+> T is converted into the Tcm. Therefore, the discovery of the vMIP-II action mechanism provides a brand-new strategy for drug research and development of HIV / SIV infected AIDS, provides a new means for adoptive immunotherapy of virus resistance and tumor resistance, and has important clinical application value.

The invention discloses a molding method of a rhesus monkey pulmonary fibrosis model, a preparation, a preparation method of the preparation, the rhesus monkey pulmonary fibrosis model and the application thereof. The molding method comprises the following steps: S1, performing subcutaneous injection of paraquat solution on rhesus monkey, and dripping bleomycin solution to trachea of rhesus monkey; S2, generating the rhesus monkey pulmonary fibrosis model. After molding is performed, the fact whether rhesus monkey molding is successful is diagnosed and the efficacy of a drug for treating pulmonary fibrosis is evaluated through the observation of the clinical symptoms, autonomic activities, feed intake, respiratory rate, haematological index, color dopplar ultrasound and lung tissue pathological results of rhesus monkey. An animal model built through the method, clinical symptoms, haematological indexes, color dopplar ultrasound and lung tissue pathological alteration are similar to lung fibrosis symptoms, moreover, compared with a model built by independently injecting paraquat or independently dripping bleomycin, a model of paraquat and bleomycin is higher in success rate and better in stability, and is applicable to the valuation of a new drug for treating lung fibrosis.

The invention discloses a method for establishing a non-human primate autoimmune cerebrospinal meningitis model and the application of the model. The specific technical scheme comprises the following steps; a machin is selected as the non-human primate experimental animals; MOG34-56(100Mug / ml) is prepared into an emulsion (MOG CFA=1; 1); after the experimental machin is anesthetized, the machin is intradermally injected with 1ml of prepared emulsion at 10 injection points; on the seventh day after the first injection, an MOG-CFA emulsion is prepared by use of the same method, and the second immune injection is performed at the same dosage and by use of the same method; the experimental autoimmune cerebrospinal meningitis model established by use of the method has the clinical characters of remission-relapse, and can be widely used to the related field of disseminated sclerosis diseases. Compared with the existing rhesus method and model, the method and the model also have the characteristics of short induction period, low cost, rich monkey resources and the like, and also have the application value which cannot be realized by rodent models.

The invention discloses a traditional Chinese medicine (TCM) composition for treating Bi pains. The composition is prepared from ginseng, rhizoma corydalis, pseudo-ginseng, nux vomica, himalayan teasel root, white paeony root, Chinese clematis root, luffa vegetable sponge, yam rhizome, prepared rhizome of rehmannia, root-bark of sessileflower acanthopanax, carapax trionycis, cortex eucommiae, cape jasmine fruit, senso, manyleaf paris rhizome, rhesus macaque bezoar, leopard bone, pine nodular branch, Chinese starjasmine stem, fructus gleditsiae abnormalis, draconis resin and daphne genkwa. Conventional auxiliary materials are added to the TCM composition to prepare clinically acceptable powder for external use, plaster, ointments, spray, liniments or tinctures according to conventional processes. The TCM composition has the functions of warming and activating meridians, promoting blood circulation to remove blood stasis, relieving swelling and pain and expelling evil-wind and removing dampness, has obvious effects on Bi pain such as pain in necks, shoulders, waists and lower extremities, rheumatism and rheumatoid pain and the like, and does not have toxic or side effect.

The invention discloses an SNP mark for evaluating a genetic background infiltration phenomenon of rhesus monkeys in cynomolgus monkeys and application of the SNP mark. The SNP mark comprises 48 SNP loci, namely SNP1-SNP48 which are respectively located at loci 151 in nucleotide sequences represented by SEQ ID NO:1-SEQ ID:NO48. By utilizing advantages of biological information techniques, the SNP mark for evaluating the genetic background infiltration phenomenon of the rhesus monkeys in the cynomolgus monkeys is developed and is applied to the evaluation of a genetic background infiltration level of the rhesus monkeys in the cynomolgus monkeys, so that the cost is greatly lowered, and the operation is simplified. By applying the SNP mark, rapid preliminary screening can be realized, the detection cost is lowered, and therefore, the standardized process of the evaluation of the genetic background infiltration phenomenon of the rhesus monkeys in the cynomolgus monkeys is promoted.

Synthetic polynucleotides encoding rhesus monkey carcinoembryonic antigen (CEA) are provided, the synthetic polynucleotides being condon-optimized for expression in a human cellular environment. The gene encoding CEA is commonly associated with the development of human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the CEA tumor-associated antigen, wherein aberrant CEA expression is associated with a carcinoma or its development. This invention specifically provides adenovial vector and plasmid constructs carrying codon-optimed rhesus monkey CEA and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.

The invention provides an isolated squirrel monkey prokineticin receptor 2 (PKR2) polypeptide containing the amino acid sequence referenced as SEQ ID NO:2; an isolated chimpanzee PKR2 containing the amino acid sequence referenced as SEQ ID NO:4; and an isolated rhesus monkey prokineticin receptor 1 (PKR1) referenced as SEQ ID NO:30. Also provided are methods of identifying PKR1 and PKR2 agonists and antagonists using the newly identified PKR2 and PKR1 polypeptides. Additionally, the invention provides an isolated rhesus monkey PK2 polypeptide containing the amino acid sequence referenced as SEQ ID NO:6, and an isolated rhesus monkey PK1 polypeptide containing the amino acid sequence referenced as SEQ ID NO:28. Nucleic acid molecules encoding the disclosed polypeptides further are provided by the invention.

The invention belongs to the fields of molecular biology and gene engineering, and relates to tumor antigen NY-ESO-1 protein originated from rhesus monkeys, coding gene, and applications thereof. The mentioned rhesus monkey NY-ESO-1 protein can be used for preparing antitumor vaccines, the gene which codes the NY-ESO-1 protein can be used for preparing antitumor nucleic acid vaccine; the antitumor vaccine or nucleic acid vaccine mentioned above can be merged into one or more cell factors or microbial components such as granular leukocyte-macrophage colony stimulating factor, gamma interferon, interleukin 2, transforming growth factor beta4 to made into immunity auxiliary agents; and the rhesus monkey NY-ESO-1 protein can be used with tumor-testicle antigen to have a combined immunization function or be made into polyvalent subunit vaccines. Furthermore, the invention also provides an immunogenicity composition or vaccine, and provides a novel method, which has a wide application prospect, for tumor immunity treatment.

The invention provides a method for preparing a rhesus monkey seizure model. The method comprises applying 0.5-0.7ml / kg of coriamyrtin to the rhesus monkey to induce the seizure. The invention also provides the application of the animal model in screening the drugs for treating the seizure. Compared with the other temporal epilepsy models, the research has the following advantages: (1) the drugs are systematically delivered by means of intramuscular injection, which is convenient to operate; (2) the seizure induction dosage is poorly correlated in the gender or age of the animal; (3) the repetition is good; (4) the electrode is convenient to install; (5) no direct mechanical damage is caused in the drain; (6) the seizure induction process is clear; and (7) the drug safety is good.

The invention provides for an immunogenic composition comprising a. a directed adjuvant comprising at least an anti-CD32 moiety linked to a TLR9 ligand and a first peptidic alpha-helix; and b. a gastrin-17 peptide immunogen linked to a second peptidic alpha-helix coiled to the first alpha-helix, which peptide immunogen is any of (i) human gastrin-17 comprising the amino acid sequence of SEQ ID 1, or a fragment thereof comprising the amino acid sequence of SEQ ID 2, or at least the 4 N-terminal amino acids of SEQ ID 2; (ii) an analog of (i), preferably of rhesus monkey or murine origin; and / or (iii) a functionally active variant of any of (i) or (ii), with one, two, three or four point mutations in the amino acid sequence of SEQ ID 2. The invention further provides a kit for producing such immunogenic composition, a vaccine comprising such immunogenic composition and its medical use, such as for treating gastrin dependent diseases.

The invention provides a VEGF-CRM197 recombinant fusion protein vaccine as well as a preparation method and application thereof. Specifically, the invention provides a VEGF truncated body VEGF1-107 antigen fragment which loses VEGF biological activity but retains immunogenicity, and the VEGF truncated body VEGF1-107 antigen fragment is fused with a diphtheria toxin mutant CRM197 for recombinant expression to form a VEGF recombinant fusion protein. After the VEGF recombinant fusion protein is combined with a liquid adjuvant for use, high-titer and high-antibody generation in mice and rhesus monkeys can be induced, and combination of VEGF-A and a receptor thereof is blocked, so that the promotion effect of VEGF-A on vascular endothelial cell proliferation is inhibited.

The invention discloses a multi-view learning method and system for rhesus monkey eye movement decision decoding, and belongs to the field of multi-view decoding in intrusive brain-computer interfaces. The multi-view learning method comprises the steps that an eye movement decision decoding model comprising a characteristic node extraction network, a reinforced node extraction network and a predicting network is established; eye movement decision direction data obtained after encoding of the local field potential and action potential of a medial frontal cortex auxiliary eye area in a rhesus monkey intrusive brain-computer interface, and one-hot encoding are input into the eye movement decision decoding model for training, and thus the trained eye movement decision decoding model is obtained; and the to-be-decoded local field potential and action potential are input into the trained decoding model, and thus a decoding result of the eye movement direction is obtained. The multi-view learning method and system are less in using limitation, low in computation complexity and suitable for decoding of action potential and local field potential signals in the intrusive brain-computer interface and other various multi-view learning scenes.

The invention provides a polypeptide for inhibiting dietary obesity. The amino acid sequence of the polypeptide is as follows: X1TX2YX3RTGR. The invention also provides application of the polypeptide. According to the polypeptide disclosed by the invention, the weight growth rate of experimental animals is reduced, subcutaneous and visceral fat deposition is reduced, occurrence and development of dietary obesity of experimental animals such as mice, rats and rhesus monkeys can be obviously inhibited by reducing appetite, and the abundance of intestinal symbiotic bacteria Akecmania of the experimental animals treated by the polypeptide is obviously improved.

The invention discloses a construction method of a rhesus monkey immunosuppression model and application of the rhesus monkey immunosuppression model in CAR-T cell implantation. 25mg / (kg / d) cyclophosphamide is combined with 2.5 mg / (kg / d) fludarabine to pre-treat rhesus monkeys, a disease model consistent with the change trend of various immune indexes under the human immunosuppression condition is established, and the reduction ranges of the white blood cell number (WBC) and the lymphocyte absolute number (LYM) in hematology exceed 50%; a flow cytometry detection result shows that CD3 is reduced by more than 40%, and the immunosuppression animal model is successfully built; the model is used for implanting CAR-T cells so as to be used for researching CAR-T immunotherapy. According to the method, the rhesus monkey immunosuppression animal model can be quickly and accurately established, sufficient immunosuppression can be ensured during CAR-T cell implantation of animals, so that CAR-T cells are alive in rhesus monkeys, and a more ideal and reliable non-human primate experimental animal model and a perfect evaluation system are provided for preclinical research of CAR-T immunotherapy.

Methods for identifying modulators of receptor activity using orthologues of human receptors are described. Additionally, a method for identifying an animal model useful in the screening of potential therapeutic agents is provided. The genes for bradykinin B1 receptors from five mammalian species, vervet monkey, rhesus macaque, tree shrew, dog and pig, as well as the genes for CXCR2 receptors from chimpanzee, gorilla, orangutan, rhesus, vervet and baboon have been cloned and characterized and are described herein.

The invention provides a reorganization pox seedling virus vaccine SARS-CoV (ADS-MVA) for preventing or treating SARS, and also the method for carrying out preventive vaccine anti-SARS-CoV infection in the body of Chinese rhesus monkey infection models. By constructing SARS vaccine using modified attenuation virus vaccine (MVA) as vector, fundamental immunity and toxic material elimination are realized on rhesus monkey. The invention can screen ideal vaccines for the prevention and treatment of SARS.

The invention discloses a method for staining and determining the titer of reovirus type 3 by a tissue half infection method, which comprises the following steps: by taking rhesus monkey kidney cells, namely LLC-MK2 cells, as indicator cells for detecting the reovirus type 3, namely Reo-3 virus, titrating the reovirus type 3 by the tissue half infection method; and judging a cytopathic effect by combining a crystal violet staining method, and finally calculating to obtain the titer of the virus. According to the determination method provided by the invention, the cytopathic effect is judged by combining a tissue half infection method with a crystal violet staining method, the cell condition can be simply and intuitively observed, the subjective influence of microscopic observation of experimenters is effectively reduced, meanwhile, the method is good in stability, the experiment result cannot be influenced by different time and different operators, and the method is suitable for popularization and application. And the repeatability is good.