4551results about "Reverse transcribing RNA viruses" patented technology

Described herein are systems and methods for automated cell transduction within a cell processing system. A system for cell processing may include a cell processing cartridge having a transduction system. The transduction system may include a fluidic manifold, one or more modules for performing a cell processing protocol, and a tube having a surface area to volume ration of between about 1,260 mm2 / mL and about 5,080 mm2 / mL. A method for cell processing may first include flowing cells through a tube of a flow cell of a cell processing cartridge for a first time period to achieve a transduction efficiency of at least 50%. Second, the method may include expanding the cells within a bioreactor module of the cell processing cartridge for a second time period.

The present invention provides a method for packaging a BaEV retroviral vector. The method includes constructing a stable BaEV retroviral packaging cell line, transfecting a retroviral vector plasmid containing a target sequence into a virus-producing cell line, where the virus-producing cell line is a HEK293T cell line or its derivative cell line, to harvest the transiently transfected and virus-producing retroviral vector, mixing it with the stable BaEV retroviral packaging cell line, and promoting the transduction of the retroviral vector into the stable BaEV retroviral packaging cell line by horizontal centrifugation. The present invention can achieve the packaging of a BAEV-type retroviral vector carrying a CD19CAR foreign gene plasmid, construct a BAEV-type retroviral vector-producing cell line, and produce a high-titer BAEV-type retroviral vector.

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.

Provided herein are lentiviral vectors comprising a mutated, heterologous envelope protein, a targeting protein, and at least one transgene for delivery to and expression by a cell characterized by the targeting protein. Also provided are methods and materials for producing the lentiviral vectors described herein, methods for transducing target cells, and cells transduced by lentiviral vectors according to the present disclosure.

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 relates to the technical field of biological medicine, in particular to a T cell receptor targeting AFP peptide, a preparation method of the T cell receptor and a companion diagnostic kit. A T cell receptor targeting an AFP peptide is provided, the sequence of the AFP peptide is FMNKFIYEI, and the T cell receptor comprises a TCR [alpha] chain variable domain and a TCR [beta] chain variable domain. Corresponding nucleic acid molecules, vectors and host cells, and methods of making T cell receptors are provided. Further provided is a companion diagnostic kit containing the cell receptor. The invention provides a better choice for concomitant diagnosis and treatment products of cells of alpha fetoprotein (AFP).

A method of treating or inhibiting a viral infection in a human subject, such as a SARS-CoV-2 infection, involves inhibiting in vivo the expression or activity of one or a combination of the subject's genes required for viral infection. Single genes or subsets of genes for inhibition of activity or expression are selected from certain identified genes. Methods of administration of certain known small molecules or other therapeutics which mimic loss of function of the identified genes are provided. Similar methods for conducting screens of host genes required for viral infection are shown.

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.

Disclosed are methods of treating a subject with a neurological disease associated with a splicing defect caused by TDP-43 proteinopathies, comprising administering to said subject an agent to increase expression levels and / or stability of hnRNP L, thereby attenuating and / or repairing the splicing defect. The disclosure also relates to nucleic acids targeting heterogeneous nuclear ribonucleoprotein L (hnRNP L), and their use.

The invention relates to the technical field of gene engineering. The invention provides a functional sequence shRNA1 (short hairpin ribonucleic acid 1) for silencing a circular RNAh-hsacirc005838, and further provides a lentiviral vector of the functional sequence shRNA1 and a construction method of the lentiviral vector. The invention also provides a lentivirus packaging titer kit containing the lentiviral vector with the functional sequence shRNA1, and also provides an application of the lentiviral vector with the functional sequence shRNA1 or the lentiviral vector with the functional sequence shRNA1 in preparation of a kit for breast cancer diagnosis. According to the invention, an interference target sequence siRNA1 is obtained by aiming at the annular target gene RNA h-hsacirc005838, then the finally obtained functional sequence shRNA1 can directly and efficiently infect cells and silence the annular RNAh-hsacirc005838 sequence, and the transfection effect is stable.

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.

The present invention relates to immune cells engineered to express chimeric antigen receptors (CARs) that specifically bind to fibroblast activating proteins (FAPs) for use in the treatment of skeletal muscle fibrosis in muscular dystrophy.

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.

The invention relates to the field of immunology, and particularly discloses a TCR combination and application thereof, the TCR combination is used for recognizing HBV antigen epitopes, the TCR combination comprises a plurality of separated TCRs, the plurality of separated TCRs form two TCR groups, and the two TCR groups comprise a first TCR group and a second TCR group; wherein the first TCR group specifically recognizes a first antigen epitope, and the amino acid sequence of the first antigen epitope is as shown in SEQ ID NO: 1; the first TCR group specifically recognizes a first antigen epitope, the second TCR group specifically recognizes a second antigen epitope, the amino acid sequence of the second antigen epitope is shown as SEQ ID NO: 2, the second antigen epitope respectively and correspondingly recognizes different antigen epitopes, the hepatitis B virus specific TCR and the epitope thereof are screened out, and an important means can be provided for treatment of TCR-T immune cells infected by hepatitis B virus.

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.

Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic coronavirus proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.

The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.

The invention discloses a double-target chimeric antigen receptor for co-expression of CD47 and IL-15, a CAR-T cell and application of the CAR-T cell, and belongs to the technical field of genetic engineering, the double-target chimeric antigen receptor comprises a single-chain antibody scFv-EGFRv III, a single-chain antibody scFv-VEGF, CD47 and IL-15; the nucleotide artificial sequence of the single-chain antibody scFv-EGFRv III is as shown in SEQ ID NO. 6; the nucleotide artificial sequence of the single-chain antibody scFv-VEGF is as shown in SEQ ID NO. 9. According to the application disclosed by the invention, by performing sequence optimization on targets EGFRvIII and VEGF, the anti-tumor effect of CAR-T cells in glioblastoma can be improved, and by integrating immune checkpoint molecules CD47 and interleukin-15, the immunosuppression function of a CD47-SIRP alpha signal channel can be locally exerted.

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.

The invention relates to the field of biological medicines, in particular to a chimeric cytokine activated receptor for activating lymphocytes by using soluble immunosuppressive molecules and application of the chimeric cytokine activated receptor in tumor treatment. The chimeric cytokine activation receptor and a chimeric antigen receptor for recognizing tumor antigens are connected in parallel to form a co-expressed polycistron structure. Wherein the chimeric cytokine activation receptor comprises an scFv structural domain, a transmembrane structural domain and a cytokine chimeric activation structural domain which specifically recognize and bind soluble immunosuppressive molecules. The CAR-NK cell can specifically recognize soluble inhibitory factors in the tumor microenvironment and improve the in-vivo and in-vitro anti-tumor efficacy of the CAR-NK cell, and can be used for treating solid malignant tumors.

The invention belongs to the technical field of biomedicine, and discloses an immortalized cell line for human kidney suspected cell carcinoma as well as a culture method and application of the immortalized cell line. The immortalized cell line for the human kidney suspected cell carcinoma, disclosed by the invention, is named as a human kidney suspected cell carcinoma cell line Loya a-710 (Homo sapiens), the classification name of the Latin name of the immortalized cell line is Chromophore sensor cell carcino: Loya a-710, and the preservation number of the immortalized cell line is CCTCC (China Center for Type Culture Collection) NO: C2025123. The human kidney suspected cell carcinoma cell line Loya-710 disclosed by the invention is used as an in-vitro model to rapidly grow in tissue culture, and mitochondrial mutation characteristics, a vesicle structure and a classical immunohistochemical marker of ChRCC are reserved. The invention provides a precious tool for further research on ChRCC heredity, molecules and biological characteristics, and also provides a powerful new model for mitochondrial diseases.

Disclosed herein are alphavirus vectors that include neoantigen-encoding nucleic acid sequences derived from a tumor of a subject. Also disclosed are nucleotides, cells, and methods associated with the vectors including their use as vaccines.

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 invention discloses an MUC1-CAR-T cell for co-expressing a BTLA / IL-18R chimeric receptor as well as a preparation method and application of the MUC1-CAR-T cell, and belongs to the technical field of biological medicines. The MUC1-CAR-T cell comprises a BTLA / IL-18R chimeric receptor and an MUC1-CAR structure, wherein the BTLA / IL-18R chimeric receptor is a BTLA MUC1 is used as a targeting molecule for CAR-T cell therapy, an extracellular domain of BTLA is connected with a transmembrane domain and an intracellular domain of an IL-18 receptor, and the co-expression BTLA / IL-18R chimeric receptor is designed. Experimental verification shows that the BTLA / IL-18R chimeric receptor can significantly improve the tumor killing ability of MUC1-CAR-T cells, can better inhibit the growth of tumors, and provides a novel immunotherapy strategy for the treatment of pancreatic cancer.

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).