76 results about "Nonhuman primate" patented technology

The construction of a non-human primate Usher syndrome disease model having USH2A gene mutation, wherein a target sequence against the mRNA of the non-human primate USH2A gene is established and a corresponding sgRNA is synthesized, then a knockout vector is constructed, the sgRNA and a Cas9 mRNA are mixed and injected into a non-human primate embryo to obtain a non-human primate embryo having USH2A gene knockout, and then by means of embryo transfer, a non-human primate having USH2A gene knockout is obtained, which exhibits symptoms of Usher syndrome. Upon detection and identification of the knockout effect, the knockout of the USH2A gene can be effectively realized in a non-human primate cynomolgus monkey embryo and cynomolgus monkeys, which provides a new and effective disease model for the diagnosis and treatment of Usher syndrome in non-human primates.

The invention relates to the technical field of non-human primate experimental animal upper limb movement ability evaluation and analysis, in particular to a non-human primate experimental animal upper limb movement ability comprehensive evaluation, data acquisition and analysis method. The comprehensive evaluation comprises the steps that upper limb comprehensive exercise ability evaluation is carried out by adopting an upper limb comprehensive exercise ability evaluation scale on the basis of upper limb feeding operation; and the upper limb coarse movement and the finger fine movement can be quantitatively evaluated. The data acquisition and analysis method comprises the following steps: S1, acquiring comprehensive movement time of upper limbs; s2, coordinate values of all key points of the upper limbs on a two-dimensional plane are obtained; s3, acquiring a 3D motion space trajectory; s4, analyzing the movement speed of the upper limb marked key points; s5, the joint angle of the elbow joint and the movement range of the palm, the elbow and the shoulder are obtained; and S6, analyzing to obtain finger key point distance change data. According to the invention, comprehensive objective evaluation and analysis of upper limb coarse movement and finger fine movement of non-human primate experimental animals can be realized.

The utility model discloses a non-contact drinking water system for non-human primates, which comprises a cage, a main line water supply unit and a branch line water supply unit, the main line water supply unit comprises a constant-pressure water source and a drinking water main pipeline, and the drinking water main pipeline is communicated with the interiors of the constant-pressure water source and the branch line water supply unit; one end of the branch water supply unit is communicated with the drinking water main pipeline, and the other end of the branch water supply unit is communicated with the interior of the cage; a water inlet hole is formed in one side of the cage, and the water inlet hole is communicated with the interior of the branch water supply unit. The non-human primate breeding device can well adapt to the breeding scale, funds and breeding technology of the non-human primates, is simple in structure, low in cost, energy-saving and environment-friendly, and can avoid breeding water supply pollution so as to be beneficial to the physical health of the non-human primates.

The invention belongs to the field of biological medicine research and development, discloses a method and a system for collecting and analyzing auditory electrophysiological data of experimental animals, and is particularly suitable for non-human primates. The method comprises the following steps: delivering a drug to a middle ear cavity through an external auditory canal, and synchronously recording auditory electrophysiological data before and after drug administration; aBR and DPOAE multi-mode detection is adopted, and the frequency range of 4 kHz to 32 kHz is covered; setting anesthesia depth and three-electrode positioning to reduce interference; optimizing the signal-to-noise ratio through noise suppression and dynamic signal superposition; an auditory threshold database is constructed, and a machine learning model is combined to judge an injured part. The system integrates a multi-modal stimulation module, a minimally invasive drug delivery device and a data analysis platform, and supports cross-species data compatibility. The accuracy of otology medicine research is remarkably improved, the surgical operation risk is avoided, and the method is suitable for gene therapy, ototoxicity screening and other scenes.

The utility model relates to the technical field of animal ability detection, and particularly discloses a non-human primate cognitive ability detection device with double functions, which comprises an experiment table, an animal box and a reward box, the animal box is used for animals to enter; the front end face of the animal box is provided with a through opening allowing the hand of an animal to stretch out. A movable baffle is arranged on the front end surface of the animal box; the baffle is used for controlling opening and closing of the port; the experiment table is arranged at the front end of the animal box; rewards for attracting animals to pick up are placed in the reward box; the award box is provided with an opening into which animals can extend; the reward box is movably arranged on the experiment table, and the direction of the opening of the reward box can be switched. According to the detection device provided by the scheme, the award box can move on the experiment table to change the distance between the award box and the animal box, and the opening orientation of the award box can be changed to adjust the experiment difficulty, so that compared with an existing experiment device, the diversity of experiments can be effectively improved, and then the effectiveness of animal cognitive ability detection is improved.

The invention relates to circRNA (Ribonucleic Acid) for coding rabies virus as well as a vaccine and application thereof, and belongs to the technical field of biological medicines. The invention relates to circRNA (Ribonucleic Acid) for coding rabies virus. The nucleotide sequence of the circRNA is shown as SEQ ID NO: 1. The circRNA comprises an SRV9 strain rabies virus G protein sequence after coding optimization, the circRNA is delivered through lipid nanoparticles to form the circRNA-LNP vaccine, powerful and lasting body fluid and cellular immune response can be induced in mice and non-human primates, and the complete protection effect can be achieved through a single dose. Compared with a traditional inactivated vaccine, the vaccine has the advantages of being rapid in production, high in heat stability, capable of inducing Th1 type immune bias and the like, is suitable for preventing rabies virus infection and has wide application prospects and popularization value.

Provided herein are TfR binding VHH polypeptides which bind to human and non-human primate TfR, conjugates thereof, and pharmaceutical compositions comprising these. Provided are also methods of use comprising administering TfR binding VHH polypeptides, conjugates thereof or pharmaceutical compositions thereof to deliver agents, including therapeutic agents, to treat a disease or disorder.

The invention discloses a spleen-targeted nano platform construction method suitable for tumor vaccination, and particularly relates to the field of vaccines.The spleen-targeted nano platform construction method comprises the steps that S1, CL15H6-DOPS LNPs, spherical polymer vesicles and erythrocyte membrane coated nano-particles are selected as spleen-targeted nano-carriers; s2, integrating an immunologic adjuvant; mn < 2 + > doped LNPs, ultrasonic response lipidosome and a CD3 antibody are selected to be coupled to serve as an integration material; s3, delivering in vivo; animal models are selected for in-vivo delivery and curative effect verification, and B16F10 melanoma mice, MC38 colon cancer mice and non-human primates are selected as the animal models respectively. By optimizing the chain length and the surface topological structure (such as spherical polymer vesicles) of the liposome, the spleen enrichment rate is remarkably increased, and the red marrow myeloid cell uptake efficiency is enhanced. By combining with common delivery of a manganese adjuvant, an STING channel is activated, secretion of type I interferon is promoted, and the proportion of antigen-specific CD8 + T cells and the tumor inhibition rate are increased.

The invention relates to a touch fluid neuron specific tracing imaging agent, a preparation method and application, and belongs to the technical field of nuclear medicine imaging, the tracing imaging agent is composed of a nerve tracer agent horseradish peroxidase (HRP), zirconium-89 isotope chelated by deferoxamine and a pharmaceutically acceptable carrier, the effective tracking window of the tracer agent is prolonged to 120 hours, and the effective tracking window of the tracer agent is prolonged to 120 hours. The multi-stage synaptic transfer period of the fluid touching neuron can be completely covered; the spatial resolution is improved by 5-8 times compared with that of traditional FDG-PET, and a fluid touching neuron cluster can be accurately presented; the in-vitro serum stability is excellent, the radiochemical purity is still larger than or equal to 80.5% within 120 hours, PET / MRI bimodal imaging can be adapted, drug administration is conducted through lateral ventricle minimally invasive injection, the probe is suitable for various animal models such as mice, rats and non-human primates, in-vivo dynamic tracing of sympathetic fluid neuron trans-synapses can be achieved on the premise that no tissue damage exists, and the probe has a good application prospect. And a key technical tool is provided for neural circuit analysis, neuroscience basic research and preclinical research of neurodegenerative diseases.

The invention relates to a barcoding method to assess transduction efficiency of AAV vectors, in particular in vivo in rodent and non-human primate.

The present invention belongs to the technical field of cell biology, and particularly relates to the application of Hippo-Yap pathway regulators in promoting the directed differentiation of induced pluripotent stem cells into pancreatic progenitor cells. The method of the present invention can efficiently obtain pancreatic progenitor cells derived from non-human primate rhesus monkeys in vitro, providing a material source for further obtaining functional pancreatic islet β cells of non-human primate rhesus monkeys, and more importantly, providing a practical basis for the autologous transplantation treatment of non-human primate diabetic animal models.

The invention discloses a sperm genome methylation detection method for safety evaluation of biological breeding crops by using primates and application, and relates to the technical field of safety evaluation of crops, the sperm genome methylation detection method comprises the following steps: dividing non-human primates into three groups, collecting sperms after long-term feeding, and extracting DNA (Deoxyribose Nucleic Acid); carrying out whole genome sequencing and quality control after bisulfite treatment; the epigenetic safety of crops is comprehensively evaluated by analyzing the methylation level of a whole genome and a functional region and functional enrichment of a differential methylation region and related genes thereof; according to the sperm genome methylation detection method for evaluating the safety of the biologically bred crops by utilizing the primates and the application, by utilizing a high-resolution WGBS technology, subtle epigenetic changes which are difficult to find by traditional toxicology can be detected, and the sperm genome methylation detection method has important significance in cross-generation reproduction effect evaluation, and has a wide application prospect. A food safety evaluation system can be perfected, and a more scientific and reliable safety interpretation basis can be established.

The invention provides a puncture device for a pharmaceutical injection test, and relates to the technical field of medical experiments, the puncture device comprises a base mechanism, the base mechanism is fixed on a forearm of a non-human primate experiment body through a first medical adhesive tape and a second medical adhesive tape, and the base mechanism is fixedly provided with an injection tube through a locking mechanism; a middle connecting pipe is installed at one end of the injection pipe, a separation non-return hose is inserted into the end, away from the injection pipe, of the middle connecting pipe, and a needle mechanism is fixedly installed at the end, away from the middle connecting pipe, of the separation non-return hose. Through the cooperation of the base mechanism, the first medical adhesive tape, the second medical adhesive tape and the silica gel pad, comfortable and stable attachment of the device to the forearm of an experimental body is achieved, pulling caused by animal movement is effectively resisted, and through rigid locking of a threaded inclined plate and a fastening nut of the locking mechanism to an injection tube clamping convex ball, the clamping convex ball can be locked more firmly. And the reliability of connection between the infusion tube and the middle connecting tube is further ensured.

The invention relates to the technical field of non-human primate cognitive testing devices, in particular to a non-human primate-based behavioral training and testing device and method. The device comprises a fixing frame, a screen unit, a grabbing rod reward unit, a sensing unit, a transition cage and a controller. Wherein the screen unit comprises a screen and a screen clamping groove, and the screen is connected with one side of the fixing frame through the screen clamping groove; the grabbing rod reward unit comprises a grabbing rod frame, a grabbing rod, a liquid conveying hose, a suction nozzle hole, a peristaltic pump and a reward liquid carrier, one side of the grabbing rod frame is fixedly connected with the other side of the fixing frame, and the grabbing rod is connected with the grabbing rod frame; the sensing unit comprises an infrared sensor unit and a camera shooting unit; the transition cage comprises a movable plate and a cage body, and the movable plate is movably connected with the cage body; the controller is in communication connection with the screen, the sensing unit and the peristaltic pump. The test efficiency can be improved, the test error is reduced, the stress response is reduced, and the experiment reliability and flexibility are improved.

This application relates to a modular non-human primate rearing cage, belonging to the technical field of animal husbandry. It includes a cage frame, a resource supply system, a hygiene and cleaning system, an activity and enrichment system, and a connection and management system. The cage frame includes a cage base, a cage top, and cage side frames. The resource supply system includes a food supply device and a water supply device detachably installed on the cage frame. The connection and management system includes a connecting channel on the cage side frames and a connecting cage door movably installed on the cage side frames for changing the opening and closing state of the connecting channel. The activity and enrichment system includes a lookout component installed on the cage side frames, a climbing component located between the lookout component and the cage base, and multiple monitoring units installed on the cage top frame. This application can improve the husbandry and management efficiency of non-human primates.

The present invention provides a flexible sensor for deep brain detection in humans and non-human primates, comprising a flexible electrode and a flexible printed circuit board (flexible PCB); wherein the flexible electrode includes an implantation end and a pad area, the length of the implantation end is 50–70 millimeters, detection sites are distributed thereon, pads are distributed in the pad area, the detection sites are used for detecting nerve signals, the pads are used for welding with the flexible PCB, and the detection sites and the pads are connected by wires; the hierarchical structure of the flexible electrode includes a base layer, a conductive layer and an insulating layer, wherein the base layer and the insulating layer are parylene flexible films, and the conductive layer is composed of a chromium layer and a gold layer. The present invention also discloses a welding method for the flexible sensor, which uses a method of spot hot melting of solder to weld the flexible electrode and the flexible PCB. This welding method can achieve precise alignment and tight connection of the solder joints, the conduction rate of the sensor is good, and it can avoid the rupture and deformation of the flexible sensor. The flexible sensor prepared by the present invention has strong flexibility, high transparency, and small implantation damage, and can detect the brain nerve signals of humans and non-human primates for a long time.

A method and system are disclosed for differentiating non-human primate induced pluripotent stem cells (NHP iPSCs) into hepatocyte-like cells through a defined, multi-stage protocol. The method includes sequentially exposing NHP iPSCs to six distinct cell differentiation media over an approximate eighteen-day period. Each medium comprises defined combinations of growth factors, small molecules, and inhibitors that direct progressive lineage specification through anterior primitive streak, definitive endoderm, posterior foregut, liver bud progenitors, hepatoblasts, and hepatocyte-like cells. Concentration ranges and exposure durations are provided for each stage, ensuring reproducibility and reducing heterogeneity across cell populations. In some embodiments, treatment with a transforming growth factor beta (TGF-β ) receptor I inhibitor during early hepatoblast specification enhances lineage fidelity. The resulting hepatocyte-like cells are validated by immunostaining and western blotting for hepatic markers. Applications include preclinical drug metabolism, hepatotoxicity assessment, and in vitro disease modeling using non-human primate–derived systems.

A method of differentiating nonhuman primate iPSCs to neurons may include providing a modified vector comprising a piggyBac vector backbone expressing a differentiation factor gene; treating the nonhuman primate iPSCs with the modified vector in medium; replacing the medium with a second medium including BDNF, NT-3, and laminin; adding medium supplemented with L-glutamine or an L-glutamine alternative, BDNF, and NT3; and producing neuronal lineage cells.

Capsid protein mutants capable of increasing the ability of AAVs to infect ocular tissue and the use thereof. A Cap mutant is obtained by replacing an amino acid sequence of an AAV capsid protein which is homologous to amino acids at positions D561 to R588 of a wild-type AAV2 capsid protein with one of the polypeptides as shown in SEQ ID NOs. 6-39. Some Cap mutants can infect a mouse retina from the RGC layer, cone and rod cells of INL and ONL, corneal limbus regions, trabecular meshwork, RPE and a small amount of RPE cells by administration via intravitreous injection, can solve the problem that it is difficult for the conventional serotype AAV to infect the cells in the posterior layer of the retina due to insufficient penetrability, and is expected to become a potential carrier for the treatment of glaucoma. Experimental data show that the abilities of some Cap mutants to infect and penetrate the retina of non-human primates are optimized, thereby providing a new tool for developing gene therapy preparations for ophthalmic diseases or constructing animal models related to ophthalmic diseases.

The utility model discloses a device for testing the lower limb muscle strength of a non-human primate animal, and the device comprises a device body which comprises an animal fixing box, the back of the animal fixing box is provided with an animal access door, and the top of the animal fixing box is provided with an animal head fixing device; through holes allowing the arms of the animals to extend out are symmetrically formed in the two sides of the animal fixing box, a muscle strength testing device and a fixing ring used for being fixed to the ankles of the animals are arranged in the animal fixing box, and the muscle strength testing device is connected with the fixing ring and used for detecting lower limb muscle strength data of the non-human primates. The lower limb muscle force data of the non-human primate animal can be accurately recorded, so that the recovery degree of the lower limb muscle force of the non-human primate animal can be scientifically and objectively observed, and objectivity, scientificity and accuracy of animal medical experiment data are facilitated.

The present invention discloses a non-human primate behavioral data acquisition device and a data acquisition method, wherein the non-human primate behavioral data acquisition device includes an animal movement device, a plurality of stereo cameras and an analysis terminal, the animal movement device includes a treadmill, a hanger, an animal restraint and a plurality of fluorescent spray paints, the hanger is set above the running belt of the treadmill, the hanger is provided with a suspension rod extending toward the running belt, the end of the suspension rod is provided with a first buckle, the animal restraint is provided with a second buckle, and the first buckle is correspondingly buckled with the first buckle; the plurality of fluorescent spray paints are used to mark the joints; the number of the plurality of stereo cameras is not less than four, and the plurality of stereo cameras are arranged at intervals in the peripheral area of ​​the treadmill to collect animal gait data and transmit the data to the analysis terminal. The present invention can effectively collect non-human primate behavioral gait data and analyze the non-human primate behavioral gait data.

The invention provides a targeting reagent for preparing fragile X syndrome animals and application of the targeting reagent. The invention discloses a target which is matched with non-human primates and is suitable for gene modification, namely a third exon and / or a fourth exon of an FMR1 gene, a target reagent is prepared by targeting the target, and a fragile X syndrome animal model with typical disease symptoms can be obtained by implementing down-regulation.

This invention discloses a neural microprobe for bimodal functional localization and precise electrical stimulation of deep brain nuclei in non-human primates. It comprises a basal layer, a conductive metal layer, and an insulating layer. The conductive layer includes a set of detection sites and stimulation sites. This invention employs a dry etching process on the back of the silicon basal layer using two insulating layers with opposite stresses, balancing the stress differences between the different materials. This overcomes the technological challenges of extending silicon microprobes and solves the problems of probe bending and low mechanical stress caused by the large aspect ratio of silicon probes in non-human primates. The detection sites acquire bimodal signals using modified nanomaterials and polymer anti-interference ion-exchange membranes as localization markers for functional localization. The detection sites are arranged between the positive and negative electrodes of the electrical stimulation, controlling the stimulation range to be near the detection sites, thus achieving precise electrical stimulation. This invention provides a new research method and means for deep brain stimulation therapy of diseases such as Parkinson's disease.

The invention relates to the field of medicines, in particular to a construction method of an Alzheimer's disease non-human primate model. A small dose of thiamine antagonist pyrithiamine is given to the chronic abdominal cavity to induce chronic thiamine metabolic disorder, so that the non-human primate marmoset Alzheimer disease model capable of reflecting the Alzheimer disease course is established, and the method has the advantages of simplicity in operation, small animal injury and the like; therefore, the method is beneficial to further basic clinical transformation research and the like, and has more important scientific significance and economic value.

The feeding barrel for the non-human primates comprises a barrel body and a barrel cover detachably installed on the barrel body, the barrel body is in a barrel shape with the top open, and the side wall of the barrel body is hollowed out so that the feeding position can be observed conveniently; the barrel cover is detachably hung on the top wall of the rearing cage, and the barrel body and the barrel cover are made of food-grade hard materials. According to the feeding barrel for the non-human primates, food is placed in the feeding barrel, so that the food is effectively prevented from being contaminated by dirt in a rearing cage; the hand and the arm of a non-human primate extend into the feeding barrel from the feeding hole for feeding, and meanwhile, the position of food is observed through the hollow structure, so that foraging is facilitated, the fun of exploring and finding in the foraging process of the non-human primate is increased, and animal welfare is increased; the barrel body and the barrel cover are preferably made of food-grade hard materials, can be effectively prevented from being damaged by non-human animals, are convenient to clean and meet the strict requirements of industries such as medicine research and development on sanitary conditions.

A method for differentiating non-human primate iPSCs into neurons may include providing a modified vector containing a piggyBac vector backbone, the modified vector expressing differentiation factor genes; treating the non-human primate iPSCs in a culture medium with the modified vector; replacing the culture medium with a second culture medium comprising BDNF, NT-3, and laminin; adding a culture medium supplemented with L-glutamine or an L-glutamine substitute, BDNF, and NT3; and generating neuronal lineage cells.

A method of differentiating nonhuman primate induced pluripotent stem cells (iPSCs) to oligodendrocytes is provided. The method may include providing a modified vector comprising a piggyBac vector backbone that expresses one or more differentiation factor genes, including SOX10, OLIG2, and NKX6-2. The piggyBac vector backbone may comprise one or more terminal inverted repeats and one or more transposase recognition sites configured to interact with a piggyBac transposase to mediate genomic integration at TTAA or noncanonical target sequences. The vector may further include a selectable marker and a promoter for regulated expression. The modified vector may be introduced into nonhuman primate iPSCs, for example from Macaca fascicularis, by electroporation and used in a feeder-free differentiation workflow. The resulting differentiated cells may be identified by expression of oligodendrocyte-associated markers including O4, O1, PDGFRA, MOG, GALC, CNPase, and myelin basic protein (MBP).

Disclosed are an antibody targeting the monkeypox virus, an antigen-binding fragment thereof, and a use thereof. The antibody or the antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region. The antibody or the antigen-binding fragment thereof of the present invention targets A35R of humans and non-human primates.

The present invention discloses a cytosine base editor based on cynomolgus monkey APOBEC3A and its mutants, belonging to the field of genetic engineering technology. A series of CBE single-base editors constructed by the present invention mainly include sgRNA, mA3A or its mutants, nCas9 (D10A), red fluorescent protein, uracil DNA glycosylase inhibitor, high copy replication origin and ampicillin resistance screening marker gene. The editing window of the single-base editor constructed by the present invention is the C3-C14 site, the editing efficiency can reach up to 75%, and the product purity can reach up to 95%. The present invention uses APOBEC3A of non-human primate cynomolgus monkey as the cytosine deaminase of the CBE system for the first time, enriching the gene editing toolkit, and providing a good idea and direction for the optimization of cytosine base editors in the future.