688results about "Interferons" patented technology

The invention discloses a grass carp gamma interferon fusion protein as well as a mutant, a coding gene and application thereof. In order to improve the expression quantity or expression efficiency of the grass carp gamma interferon, codon optimization and mutation are carried out on the coding gene of the grass carp gamma interferon to obtain the grass carp gamma interferon mutant. The fusion protein is further obtained by connecting the grass carp gamma interferon mutant with the C end of the grass carp ferritin heavy chain subunit of which the last 17 amino acids are removed through a connecting peptide. In order to further improve the antiviral activity of the fusion protein, the obtained fusion protein is subjected to single-point mutation, and the titer of the fusion protein is remarkably improved. The fusion protein is expressed by a silkworm cell eukaryotic expression system, and the fusion protein shows a conformation suitable for the interferon to play functions based on the ferritin self-assembly characteristic, so that the titer of the interferon in a host is effectively improved, and the in-vivo and in-vitro half-life period of the interferon is prolonged. The invention has application prospects in preparation of drugs or reagents for preventing or treating viral diseases of grass carp and the like.

The present invention relates, in part, to chimeric proteins comprising consensus interferon, or a variant thereof, and their use as therapeutic agents.

Disclosed herein are extracellular vesicles comprising an immunomodulating component. Also provided are methods for producing the extracellular vesicles and methods for using the extracellular vesicles for treating cancer, GvHD, and autoimmune diseases.

The invention relates to a repetitive structural unit recombinant protein cpE2 and a preparation method and application thereof. The recombinant protein cpE2 of the repetitive structural unit has self-assembly performance and is formed by modifying an E2 subunit of a pyruvate dehydrogenase compound and dihydrofatty acid amide transacetylase. Specifically, the C end of the E2 protein is arranged at the N end through a connecting peptide by utilizing a circulating recombination principle, so that the recombinant protein cpE2 is constructed. The engineered cpE2 protein cage can be self-assembled into a cage-shaped structure, linking groups can be respectively brought into the protein cage through N-terminal or C-terminal modification of cpE2, the problem that a modifier or a drug is difficult to put into the protein cage by a traditional E2 protein is solved, meanwhile, the specific particle size of the cpE2 protein cage can be controlled through the length of a linking peptide, and the protein cage has a good application prospect. And efficient carrying of goods is achieved.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

The present invention relates to the field of genetic engineering technology, specifically disclosing a raccoon dog interferon-α and β-defensin fusion protein, its encoding gene, and its application. The raccoon dog interferon-α and β-defensin fusion protein has the amino acid sequence shown in SEQ ID NO:1. The present invention also provides a gene encoding the fusion protein, a recombinant expression vector, and a host cell. The fusion protein provided by the present invention possesses the dual biological activities of raccoon dog interferon-α and β-defensin, and has certain antiviral and antibacterial activities.

The present invention relates to an improved process for producing a product comprising a protein of interest (TP) capable of crystallizing under salt soluble conditions by crystallization of said TP. The present invention uses at least two different TP-containing protein feeds, which are mixed to produce a supersaturated protein solution in which TP crystallizes. One of the protein feeds must have a pH at least plus 0.1 to the pH (pHMCY, TP) providing the maximum crystallization yield of the TP, and one of the protein feeds must have a pH at most minus 0.1 to the pHMCY, TP.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

Disclosed are a bispecific recombinant protein and a use thereof. The bispecific recombinant protein comprises a first functional binding region, a second functional binding region and an Fc region; the first functional binding region comprises a first chain and a second chain, and a C-terminus of the first chain and a C-terminus of the second functional binding region are separately connected to an N-terminus of the Fc region directly or by means of a linker sequence; and a C-terminus of the second chain is connected to an N-terminus of the second functional binding region directly or by means of a linker sequence. Further disclosed is an application of the recombinant protein in terms of anti-tumor, anti-virus, liver disease treatment, and other applications. The recombinant protein may significantly improve the killing efficacy of target cells while significantly reducing toxic side effects caused by binding to non-target cells, and has good safety and good freeze-thaw stability.

Provided are a method for diagnosing cancer, a diagnosis kit and compositions useful for measurement of NK cell activity. The incidence of cancer may be diagnosed by monitoring changes in the in vivo immune system through measurement of NK cell activity in blood. Thus, the incidence of cancer may be readily predicted as described herein using a blood sample from a subject.

Provided is an mRNA vaccine, said mRNA vaccine containing an immune cell targeting molecule that is expressed in fusion with an antigen and enhances the immunological effectiveness of an mRNA vaccine.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

The invention provides an anti-tumor modification method of stem / progenitor cell-derived neutrophil, which comprises the following steps: extracting mouse bone marrow-derived Lin-progenitor cells and human umbilical cord hematopoietic stem / progenitor cells, modifying ER-Hoxb8 progenitor cells by gene editing, and inducing the ER-Hoxb8 progenitor cells into neutrophil; three modification strategies of chimeric antigen receptor CAR gene engineering modification, high expression MET gene modification and high expression of IFN-gamma while the TGFBR2 gene is stably knocked out are respectively adopted, and the anti-tumor phenotype of the neutrophil N1 is maintained. Compared with the prior art, the engineering neutrophile granulocyte has the following advantages that the engineering neutrophile granulocyte prepared by the method has the advantages of infinite sources, long-time preservation, safety, controllability, efficient and rapid preparation and the like; the engineered neutrophil can maintain the N1 antitumor phenotype and promote the antitumor function; the immunosuppression microenvironment of the solid tumor can be improved and the treatment effect can be improved by singly using or combining the immune checkpoint inhibitor.

The present disclosure relates to T cells engineered to comprise a heterologous nucleic acid sequence encoding a double mutant transforming growth factor [beta] 1 (dmTGFB1) under the control of a promoter sequence. In certain embodiments, the cells further comprise modifications of an endogenous nucleic acid sequence encoding TNFA, e.g., knockdown; modifications, e.g., knock-down, of an endogenous nucleic acid sequence encoding IFNG or IL17A; and insertion of sequences encoding regulatory T cell promoting molecules, and compositions and uses thereof.

The present disclosure provides genetically modified iPSC-derived γδT cells and their precursors. A double genomic disruption in the suppressor of cytokine signaling 1 (SOCS1) gene and the cytokine-inducible sh2-containing protein (CISH) gene are provided, as is a triple genomic disruption in genes for SOCS1, CISH, and Bcl-2 interacting mediator of cell death (BIM), as is a quadruple genomic disruption in genes for SOCS1, CISH, BIM, and cell surface death receptor (FAS), as is a quintuple genomic disruption in genes for SOCS1, CISH, BIM, β-2-Microglobulin (B2M), and class II transactivator (CITTA), as is a sextuple genomic disruption in genes for SOCS1, CISH, BIM, B2M, CITTA, and FAS. Also provided is genetically modified iPSC-derived γδT cells and their precursors with improved proliferation and tumor killing activity. Also provided are genetically modified iPSC-derived γδT cells and their precursors further comprising CD19 CAR. The present disclosure further provides methods making and using such cells, as well as gene editing systems.

This disclosure provides a method of preventing, alleviating, or treating a condition (i.e., neutropenia) in a patient in need thereof, the condition characterized by compromised white blood cell production in the patient. The method includes administering to the patient a therapeutically effective amount of a protein complex comprising a modified human granulocyte-colony stimulating factor (hG-CSF) covalently linked to an immunoglobulin Fc region via a non-peptidyl polymer. The non-peptidyl polymer is site-specifically linked to an N-terminus of the immunoglobulin Fc region, and the modified hG-CSF comprises substitutions in at least one of Cys17 and Pro65.

The invention relates to the field of biological medicine and aquatic products, and discloses a grass carp IFNf interferon and truncated protein and application thereof in virus resistance or bacterium resistance. The applicant discovers the new subtype IFNf of the grass carp interferon for the first time, the protein coded by the new gene has an efficient antiviral effect, and the derived peptide AMP-G2 of the grass carp interferon has broad-spectrum antibacterial activity. The sensitivity of the grass carp interferon IFNf to grass carp reovirus (GCRV) infection is higher than that of other interferon, and the grass carp interferon IFNf shows obvious antiviral activity on the cellular level and can be used for preparing antiviral drugs. The interferon-derived peptide provided by the invention is a host natural peptide, is small in molecular weight and simple to synthesize, has a remarkable bactericidal effect on various bacteria and fungi, and can be used for preparing broad-spectrum antibacterial agents or antibacterial drugs.

The invention belongs to the technical field of cell biology, and particularly relates to a preparation method of tumor enhanced targeting and therapeutic function extracellular vesicles and a chip device. The invention firstly provides an integrated chip device which is provided with a cell screening module and a functional preparation module and comprises a plurality of functional layers, wherein one functional layer is provided with a cell evolution screening area with gradient for cell screening, and the other functional layer is provided with a cell electric remodeling area for cell functionalization transformation. The invention innovatively proposes that tumor cells with strong metastasis ability are screened based on culture gradient, the tumor cells with stronger invasion ability are distinguished by utilizing spatial segmentation, then the screened cell subpopulation is transferred to a cell electric remodeling area in combination with overturning operation of the chip, and the cell subpopulation is transferred to the cell electric remodeling area in a manner of focusing an electric field through nanopores. And meanwhile, therapeutic molecules are efficiently delivered to realize cell transformation, so that the transformed cells can enhance the output of extracellular vesicles with a therapeutic function.

The invention belongs to the technical field of veterinary medicine, and provides a co-expressed recombinant porcine alpha and gamma interferon. The I-type interferon alpha and the II-type interferon gamma not only exert the anti-virus, anti-cell division and immune regulation effects of the interferon, but also can activate T cells and natural killer cells, and fully exert the multiple activities of the interferon. The two interferons are co-expressed in insect cells, the expression protein can be folded and then processed and modified, the structure of the expression protein is closer to a natural structure, the biological activity is high, the recombinant protein is easy to purify, the production scale is easy to expand, and live viruses or potential dangerous pathogens do not need to be treated, so that the production cost is reduced; by optimizing the production process and fermentation conditions, the quality and stability of the recombinant protein can be further improved.

The present disclosure provides genetically modified iPSC-derived γδT cells and their precursors. A double genomic disruption in the suppressor of cytokine signaling 1 (SOCS1) gene and the cytokine-inducible sh2-containing protein (CISH) gene are provided, as is a triple genomic disruption in genes for SOCS1, CISH, and Bcl-2 interacting mediator of cell death (BIM), as is a quadruple genomic disruption in genes for SOCS1, CISH, BIM, and cell surface death receptor (FAS), as is a quintuple genomic disruption in genes for SOCS1, CISH, BIM, β-2-Microglobulin (B2M), and class II transactivator (CIITA), as is a sextuple genomic disruption in genes for SOCS1, CISH, BIM, B2M, CIITA, and FAS. Also provided is genetically modified iPSC-derived γδT cells and their precursors with improved proliferation and tumor killing activity. Also provided are genetically modified iPSC-derived γδT cells and their precursors further comprising CD19 CAR. The present disclosure further provides methods making and using such cells, as well as gene editing systems.

The invention belongs to the technical field of biology, and particularly relates to a fusion protein IFN alpha-gE-Fc and application of the fusion protein IFN alpha-gE-Fc in preparation of a recombinant varicella-herpes zoster vaccine. The IFN alpha-gE-Fc fusion protein is constructed, gE is dimerized through the Fc segment of human IgG, the stability and size of the protein can be improved, and effective LN targeting and dendritic cell capture are promoted. In order to further increase the treatment and presentation of DCs on antigens, cell factors IFN alpha are fused at the N end of gE-Fc to induce strong cellular immune response and humoral immunity at the same time, no exogenous sequence is introduced, cellular immune response can be effectively enhanced, the defects of traditional adjuvants are overcome, and the immunologic adjuvant has a good application prospect. A candidate vaccine is provided for developing a safe and effective herpes zoster vaccine.

The present invention belongs to the field of immunology and relates to proteins and polypeptides comprising an immunoglobulin single variable domain (ISVD) fused with a cytokine. In particular, the present invention provides a chimeric protein which comprises an immunoglobulin single variable domain (ISVD) fused with a cytokine, wherein an internal fusion site of the ISVD is linked to the cytokine, wherein the internal fusion site is located in a loop or turn between two secondary structure elements. The fusion of the cytokine to the ISVD upon binding to the cytokine receptor or receptor subunit(s) allows for the modulation of the cytokine receptor activity and / or downstream signaling.

The invention provides a bovine interferon alpha recombinant protein with a long half-life period, a variant protein and an application of the bovine interferon alpha recombinant protein and the variant protein in virus resistance, a key part with an antiviral effect of BoIFN alpha and a key part with a low toxicity effect of BoIFN tau are connected by using a flexible linker to construct a low-toxicity long-acting interferon, and specific amino acid of the low-toxicity long-acting interferon is subjected to site-specific mutagenesis on the basis of the low-toxicity long-acting interferon; the toxicity and the half-life period are further improved. Tests prove that the long-acting recombinant bovine interferon product prepared by the invention is an efficient, long-acting and broad-spectrum antiviral drug product, has a longer half-life period and higher biological activity than common natural bovine interferon or hybrid interferon, prolongs the half-life period, improves the biological activity, reduces the preparation cost of an interferon preparation, and is suitable for industrial production. The compound has huge potential and value of being developed into broad-spectrum antiviral drugs and veterinary clinical application.

The present invention provides a combination therapy for treating a tumor in a subject. The combination comprises two elements. The first is a polypeptide construct comprising an attenuated Type I interferon (IFN) linked to an antibody which binds to a cell surface-associated antigen expressed on the tumour cell and comprising a functional Fc region. The second is a CD47 antagonist which inhibits the interaction CD47 with the SIRPα receptor.

The present invention relates, in part, to chimeric protein complexes comprising an anti-Clec9A targeting moiety, a modified Fc domain, and a modified human IFNα, and their use as therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the chimeric protein complexes and their use in treating various diseases.

The presently disclosed subject matter relates to tumor infiltrated T cells induced by oncolytic virus (“OV-induced T cells”), methods of making and using said OV-induced T cells for an adoptive T-cell therapy. The presently disclosed subject matter further relates to oncolytic viruses and armed oncolytic viruses, methods of making and using said oncolytic viruses, as well as pharmaceutical compositions and kits comprising said oncolytic viruses.

Disclosed are a recombinant interferon drug targeting a conserved HIV gp41 subunit membrane-proximal external region (MPER) and a use thereof. Specifically, disclosed is a targeted interferon fusion protein ZP-IC, comprising a 10E8 antibody or an antigen-binding fragment thereof, and an integrated interferon α, wherein the 10E8 antibody or the antigen-binding fragment thereof is linked to the integrated interferon α by means of a linker. In the present invention, the 10E8 antibody capable of identifying a highly conserved gp41 subunit MPER of an HIV envelope glycoprotein is used as a targeting tool for the integrated interferon. Therefore, a target exposed by a conformational change of a viral envelope protein during the infection of a cell can be accurately identified, viral infection is prevented, and a neutralizing effect is exerted; and in addition, a carried interferon molecule can more effectively bind to an interferon receptor on a cell around the HIV virus and achieve an antiviral role. Experiments have demonstrated that the ZP-IC has excellent antiviral activity and the capability of inhibiting an overwhelming majority of HIV strains across a broad spectrum.

The present invention discloses a preparation method and application of a bacterial bionic vesicle for reprogramming macrophages. The preparation of the bacterial bionic vesicle is to first fuse the bacterial outer membrane anchor protein with the IFN-γ gene, and then use high-pressure homogenization technology to drive genetically engineered bacteria to extrude from the cracks and self-assemble into bacterial bionic vesicles modified with IFN-γ surface. In vitro, the bacterial bionic vesicles of the present invention can promote the reprogramming of M1 macrophages into M2 macrophages, and release nitric oxide to directly kill tumor cells. In vivo, the bacterial bionic vesicles can efficiently enrich in the tumor area by virtue of their nanosize, reprogram the tumor-promoting M2TAMs to the tumor-killing M1TAMs and coordinate adaptive immunity to jointly inhibit tumor growth. In short, the bacterial bionic vesicles of reprogramming macrophages of the present invention are a powerful immunomodulator, which significantly inhibits tumor growth in a variety of tumor models and is of great significance in the immunotherapy of tumors.