2872results about "Reverse transcribing RNA viruses" patented technology

The invention provides an UTR (Untranslated Region) element H2202 P1-G as well as a construction method and application thereof, and relates to the technical field of mRNA (messenger ribonucleic acid). According to the present invention, the ribosome load prediction and the secondary structure optimization are performed on the natural 5 'UTR of the HIV TAT 202 gene through the BaidleHelix platform, and the obtained HTAT 202 P1 sequence avoids the inhibitory hairpin structure so as to significantly improve the luciferase expression quantity compared to the natural UTR; an ncRNA sequence without a secondary structure is introduced on the basis of the HTAT 202 P1, translation inhibition of a 5 'cap region is further relieved, and the protein expression quantity of the constructed H2202 P1-G mutant (the DNA sequence of the H2202 P1-G is as shown in SEQ NO 1, and the RNA sequence is as shown in SEQ NO 2) is further improved.

The invention provides an enhancer RNA (Ribonucleic Acid) molecule MZGAe1 and application thereof, and relates to the technical field of biology. The invention provides an enhancer RNA (Ribonucleic Acid) molecule MZGAe1. The nucleotide sequence of the enhancer RNA molecule MZGAe1 is as shown in SEQ ID NO: 1; meanwhile, the invention further provides a specific sgRNA sequence for activating the molecule in a targeted manner and a recombinant vector of the specific sgRNA sequence. Expression of endogenous MZGAe1 of cells is specifically activated by adopting a CRISPR activation technology, and conversion of mouse embryonic stem cells to bicellular-like cells can be efficiently promoted. By providing a brand-new endogenous targeted MZGAe1 accurate activation tool, the efficient transformation of wild mouse embryonic stem cells to bicellular cells can be realized only under the condition of endogenous activation of single enhancer RNA molecule MZGAe1, the proportion is at least increased by 5%, the expression of a totipotent marker gene ZSCAN4 is activated, and the expression of the totipotent marker gene ZSCAN4 is promoted. And an efficient and specific brand-new research tool and scheme are provided for researching zygote genome activation, embryonic development early events and cell reprogramming.

The invention discloses a hybridoma cell strain, a monoclonal antibody, a linear epitope antigen and application thereof, and relates to the field of genetic engineering, in particular to a hybridoma cell strain, a monoclonal antibody, a linear epitope antigen and application thereof. The preservation number of the hybridoma cell strain P27-A1 is CGMCC (China General Microbiological Culture Collection Center) No. 46352. The hybridoma cell strain P27-A1 is prepared from feline leukemia virus p27, and a monoclonal antibody secreted by the hybridoma cell strain P27-A1 recognizes a linear epitope antigen of feline leukemia virus p27 protein; the kit for the feline leukemia virus p27 comprises the monoclonal antibody A1 secreted by the hybridoma cell strain P27-A1. The monoclonal antibody secreted by the hybridoma cell strain can greatly improve the sensitivity of the p27 protein for detecting feline leukemia virus. The invention provides the monoclonal antibody secreted by the hybridoma cell strain for identification, and the monoclonal antibody can be used for preparing a diagnostic kit such as a colloidal gold test strip.

The invention discloses an anti-TP53 mutation T cell receptor and application thereof, the T cell receptor comprises specific alpha chain and beta chain variable domains, and the complementary determining region (CDR) sequence is shown as SEQ ID NO: 9-14. The TCR has the core advantage that the TCR has excellent broad-spectrum recognition capability, can target six different amino acid substitutions (A, G, I, N, S and T) at the R249 site, and effectively deals with tumor heterogeneity and mutation difference between patients. Aiming at high-frequency HLA-B * 07: 02 alleles in people, the TCR lays a foundation for developing TCR-T cell therapy covering a wide range of people, and has great clinical application value and market potential in treatment of various solid tumors carrying TP53 R249 hotspot mutation, such as liver cancer.

This disclosure generally relates to methods and compositions for eliciting broad and robust immune responses to a protein of interest. The methods employ both DNA and RNA-based vaccines that encode at least a portion of the protein of interest.

Compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and / or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

Disclosed are a therapeutic agent comprising a labeling polypeptide introduced into a tumor cell and a multispecific antibody capable of binding to and recognizing the labeling polypeptide, the multispecific antibody, a kit comprising the therapeutic agent, and use of the therapeutic agent or the multispecific antibody in the manufacture of a medicament for treating a tumor and / or a cancer.

Provided herein are chimeric cytokine receptors bearing a binding domain capable of binding a TGF-β ligand or a TGF-β receptor antibody. When present on chimeric antigen receptor (CAR)-bearing immune cells (CAR-T-cells), such receptors allow for increased CAR-T cell expansion, activity and persistence, constitutively and / or through engagement of a TGF-β ligand or a TGF-β receptor antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.

The invention relates to the fields of biology, medicine and clinic. In particular to application of PAICS as a target spot in developing or screening reagents for preventing and / or treating orthopoxvirus infection, and application of inhibiting a synthetic pathway of purine nucleotide and / or inhibiting a metabolic pathway of folic acid in preparing reagents for treating and / or preventing orthopoxvirus infection diseases. In order to restrain the infection of orthopoxvirus, the inventor team uses a CRISPR / Cas9 technology to carry out generic genome screening on host cells infected by orthopoxvirus, determines a host-dependent gene PAICS gene in the orthopoxvirus infection process, and verifies and clarifies the virus-dependent mechanism of the gene; in order to deal with the global continuous orthopoxvirus infection problem, the invention plays an important role in the development and screening of future related prevention or treatment drugs, and also expands the new clinical application of existing drugs including methotrexate, mercaptopurine, mizoribine and the like.

The invention relates to the technical field of cell engineering, and particularly discloses a construction method and application of a sika deer immortalized renal epithelial cell line, and the construction method comprises the following steps: taking renal epithelial primary cells from healthy sika deer renal cortex tissues to obtain primary renal epithelial cells; treating the primary renal epithelial cells with trypsin to obtain a cell suspension; inoculating the cell suspension into a complete culture medium, and transfecting with lentivirus loaded with SV40 large T antigen genes to obtain transfected cells; 3 [mu] g / mL puromycin is applied to the transfected cells for selective culture, so that non-transfected cells are eliminated, and drug-resistant cells are obtained; carrying out continuous passage on the drug-resistant cells for at least 30 generations to obtain the immortalized renal epithelial cell line of the sika deer; according to the invention, through a specific action mechanism (inhibiting a p53 / pRb pathway and blocking cell cycle exit) of the SV40 large T antigen, a proliferation limit caused by inhibition of telomerase activity of primary cells of the cervidae animals is overcome, and a cell resource library capable of realizing continuous passage is established.

The invention relates to a method for carrying out gene editing on a TRAC gene locus. Specifically, the invention provides sgRNA targeting and guiding nuclease to efficiently cut a TRAC gene, a method for modifying a CAR-T cell by using the sgRNA, the CAR-T cell obtained by the method, and a related gene editing system, reagent and kit. According to the CAR-T cell, the immunogenicity is reduced, the risk of graft versus host disease and immunological rejection can be effectively reduced, and meanwhile the killing capacity of tumor cells of the CAR-T cell is not affected.

The present application provides chimeric proteins comprising an antibody moiety that specifically binds to a component of an influenza virus or a variant thereof, and a positively charged mucoadhesive peptide fragment. Compositions comprising the chimeric proteins described herein are useful for preventing or treating an infection caused by an influenza virus or a variant thereof in an individual.

The present disclosure relates to methods for the production of a cell-based product based on using synthetic promoters or a cellular input-output unit thereof, configured for controlling the expression of at least one nucleic acid sequence of interest, upon sensing dynamic cellular- and / or environmental- state and / or condition, that leads to a desired phenotype of the cells. The present disclosure further provides cell-based products, in particular, animal cell-based meat products (ACBM).

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof in the central nervous system or ex vivo. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a disease (e.g., a neurological disease), preventing a disease (e.g., neurological disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof.

The invention belongs to the technical field of biological medicine, and particularly relates to an engineered cell microvesicle and a delivery system based on the engineered cell microvesicle, the system realizes efficient preparation of 1-5 [mu] m cell microvesicles, and the cell microvesicles have a large space volume and can be used for preparing the cell microvesicles. The carrier can be used for loading and delivery of target protein, polypeptide and recombinase which are specifically expressed in mother cells. The system transfects mother cells through lentivirus transfection or plasmid transfection to further produce cell microvesicles, and the microvesicles can load more goods and inherit membrane proteins of the mother cells, and can also effectively load intracellular proteins to realize effective delivery. By virtue of good structural stability, high immunogenicity and excellent biocompatibility, the cell microvesicle reduces systematic toxic and side effects of a traditional carrier, is expected to become an effective drug delivery system, and has great application potential in the field of gene therapy.

To provide novel transduction enhancers and uses thereof.SOLUTION: The present invention relates to a method for transducing a target cell, the method comprising the step of contacting a target cell with a retroviral vector and a compound capable of enhancing transduction efficiency or a combination of such compounds, wherein the target cell is pre- and / or co-stimulated by pre- and / or co-incubation with a transduction enhancing compound or a combination of transduction enhancing compounds prior to and / or during contacting the target cell with the retroviral vector.SELECTED DRAWING: None

Genetically engineered immune cells, which express at least two metabolism modulating polypeptides and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide or a chimeric antigen receptor (CAR) polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered immune cells for inhibiting cells expressing a target antigen in a subject in need thereof.

This invention provides vectors (e.g., lentiviral vectors) and expression cassettes for incorporation into vectors for expressing an alpha-globin (α-globin) gene. In certain embodiments method of treatment using such vectors are provided.

Compositions comprising microalgal extracellular vesicles (MEVs) formulated for intranasal delivery are provided, whereby upon intranasal administration, the MEVs are transported by a specific route, to specific regions in the brain via the olfactory nerve after intranasal administration, and to interconnected brain regions through the lateral olfactory tract (LOT). The MEVs are transported via neuronal axonal transport. The MEVs have the ability to cross synapses including: (i) synapses between olfactory sensory neurons (OSNs) and mitral / tufted neurons; (ii) synapses between mitral / tufted neurons and local neurons in multiple brain regions colonized by the lateral olfactory tract (LOT); and (iii) synapses between neurons in brain regions colonized by the LOT and neurons from the frontal cortex, hippocampus, thalamus, and hypothalamus. The compositions contain extracellular vesicles (MEVs) from microalgae loaded with bioactive cargo for the treatment, detection, diagnosis, or monitoring of diseases, disorders, or conditions of or involving the brain, particularly neuronal delivery of the cargo. The compositions and methods have multiple applications as therapeutic and diagnostic agents for the treatment, diagnosis, and monitoring of diseases, disorders, or conditions of or involving the brain. The compositions can be used in methods and uses for the treatment of cancers involving the brain, and can be used, for example, to deliver therapeutic agents for psychiatric diseases, disorders, conditions, and to deliver therapeutic agents for neurodegenerative diseases, disorders, and conditions.

A chimeric autoantibody receptor (CAAR) that enables targeting of an immune cell to autoantibody producing B cells. The CAAR includes an autoantigen or fragment thereof that is bound by autoantibodies associated with neurological autoimmune disease primarily targeting the central nervous system. Also disclosed is a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), the nucleic acid sequence encoding an autoantigen or fragment thereof that is bound by autoantibodies associated with a neurological autoimmune disease primarily targeting the central nervous system, a transmembrane domain, and an intracellular signaling domain, a vector comprising a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), a genetically modified immune cell comprising the nucleic acid molecule encoding the CAAR and use of the immune cell in the treatment or prevention of a neurological autoimmune disease primarily targeting the central nervous system, such as an autoimmune encephalopathy or encephalomyelopathy, preferably anti-NMDAR encephalitis.

Among other things, provided herein are systems that replace the natural random integration activity of a retrovirus with site-specific integration machinery. This approach allows for a more precise targeting of a gene of interest into a human genome, e.g., for therapeutic purposes. The system may include integration-deficient retrovirus (e.g., lentivirus) (IDLV), in which the natural integration activity has been reduced (e.g., by mutation to the viral integrase polypeptide). Instead, the system may comprise a site-specific recombinase (e.g., a serine recombinase, e.g., a serine integrase) capable of directing insertion of a template DNA, or portion thereof, into a desired site in the human genome.

The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (IL15) payloads, as well as compositions and methods of use thereof.

This disclosure relates methods for expanding γδ T cells. More specifically, the disclosure relates to methods of expanding γδ T cells that have an eliminated or reduced expression of endogenous MHC Class I molecules, by expressing a single-chain fusion HLA Class I protein. In some embodiments, the endogenous B2M gene of the γδ T cells is disrupted. In some embodiments, the single-chain fusion HLA Class I protein includes at least a portion of B2M protein and at least a portion of HLA-E heavy chain.

Compositions containing a nucleic acid nanostructure having a desired geometric shape and an antigen and / or immunostimulatory agent(s) bound to its surface are provided. The nanostructure design allows for control of the relative position and / or stoichiometry of the immunostimulatory agent(s) bound to its surface. The antigen and / or immunostimulatory agent(s) displayed on the nanostructure surface are arranged with the preferred number, spacing, and 3D organization to elicit a robust immune response. The displayed antigen can be eOD-GT8. The immunostimulatory agent can be, e.g., T cell epitope such as a pan HLA DR-binding epitope (PADRE) and / or a lectin such as MBL or C3, or ligand thereof such as a glycan including mannose. Also provided are antigen-T cell epitope fusions such as eOD-PADRE and nanostructures presenting the same. The immunostimulatory compositions may thus be useful as immunogens, vaccines, adjuvants, and the like. Methods of inducing immune responses are also provided.

Provided herein are methods and related compositions for enhancing or enhanced partial reprogramming of target cells in a subject in need thereof (e.g., a human subject suffering from or at risk of a disease), the method comprising administering a plurality of mesenchymal lineage progenitor or stem cells (MLPSCs), exosomes derived therefrom, or conditioned culture media derived therefrom to a subject that expresses or will express one or more reprogramming factors in a population of target cells, whereby a plurality of the target cells in the subject become partially reprogrammed, but not fully reprogrammed.

The Human Immunodeficiency Virus (HIV) infection and recurrent infection prevention mRNA vaccine comprising epitopes of HIV-1 and HIV-2 viruses and their corresponding Nef proteins.

Disclosed herein are immune cells expressing engineered cytokine receptor switches which, upon activation, can direct differentiation of the immune cells. The present disclosure further provides compositions and methods for transfecting, expanding, and activating these immune cells, including substrates which activate the engineered cytokine receptor switches disclosed herein.

The invention discloses a bipeptide modified bionic nano-vesicle as well as a preparation method and application thereof, and belongs to the field of biological medicines. The dipeptide modified bionic nano-vesicle comprises nano-particles formed by PLGA (poly (lactic-co-glycolic acid)), and the nano-particles are loaded with a medicine with a nerve protection or nerve repair effect; the surface of the nanoparticle is coated with a macrophage membrane for expressing RVG peptide and T7 peptide. The bipeptide modified bionic nano-vesicle simultaneously presents T7 peptide and RVG peptide through an engineered macrophage membrane, the T7 peptide is combined with a blood-brain barrier transferrin receptor through high affinity to realize efficient brain entry, astrocytes in the brain are specifically recognized by virtue of the RVG peptide, accurate recognition and delivery of target cells in a focus area are realized, and the bipeptide modified bionic nano-vesicle has a good application prospect. Meanwhile, the natural inflammation tropism and immune escape ability of a macrophage membrane are reserved, and the problems that a traditional drug delivery system is low in targeting precision, and cross-barrier distribution and intracerebral distribution are difficult to cooperate are solved.

Disclosed is a composition for treating dystrophic epidermolysis bullosa, the composition containing, among other things, a composition which includes cells that are derived from the lesions of dystrophic epidermolysis bullosa patients and that have been genetically engineered such as to produce type VII collagen.