7892results about "Fusion polypeptide" patented technology

The invention provides a polypeptide or a derivative and a pharmaceutically acceptable salt thereof. The amino acid sequence of the polypeptide is as shown in SEQ ID NO: 1. The polypeptide or the derivative and the pharmaceutically acceptable salt thereof disclosed by the invention can be combined with GLP-1R and GCGR, and is used for effectively activating the GLP-1R and the GCGR. Therefore, the polypeptide or the derivative and the pharmaceutically acceptable salt thereof can be used for detecting GLP-1R and / or GCGR, and can also be used for treating or preventing GLP-1R and / or GCGR related diseases (such as metabolic disorder related diseases, such as obesity, diabetes, fatty liver diseases, non-alcoholic fatty liver diseases and the like).

The present invention discloses a human serum albumin-targeting nanobody and its application. A variety of human serum albumin-targeting nanobodies that can be used to construct long-acting fusion protein drugs and their immune screening methods are disclosed. The antibody is composed only of the heavy chain variable region and can be fused and expressed with therapeutic proteins or polypeptide drugs such as interleukin, interferon, and tumor necrosis factor in an Escherichia coli expression system. The fusion protein has the activity of specifically binding to human serum albumin, has a relatively high affinity, can effectively extend the drug half-life, and does not affect the biological activity of the recombinant protein drug at the same time.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

The invention provides a polypeptide or a pharmaceutically acceptable salt of the polypeptide. The amino acid sequence of the polypeptide is as shown in HSQGTFTSDYSKYLEEAAAAEFVAWLLAGG. The invention further provides a preparation method of the polypeptide. The polypeptide or the pharmaceutically acceptable salt thereof can be combined with the GLP-1R and is used for effectively activating the GLP-1R. Therefore, the polypeptide or the pharmaceutically acceptable salt thereof can be used for effectively treating metabolic disorder related diseases (such as obesity, diabetes, dyslipidemia related diseases, fatty liver diseases, metabolic syndromes and non-alcoholic fatty liver diseases).

The present disclosure concerns a fusion polypeptide for making acetyl-phosphate from glucose, a recombinant yeast host cell expressing the fusion polypeptide as well as methods of using the fusion polypeptide. The fusion polypeptide comprising (i) a glucose-6-phosphate isomerase moiety and (ii) a phosphoketolase moiety.

The invention belongs to the technical field of nano antibodies, and particularly relates to a nano antibody specifically bound with AAV9 and application of the nano antibody. The nano antibody provided by the invention can be specifically combined with the AAV9 adeno-associated virus without being combined with other AAV serotypes such as AAV2, AAV5 and AAV8, so that high-sensitivity and high-specificity detection of the AAV9 adeno-associated virus is realized. In practical application, the nano-antibody coupled solid-phase carrier provided by the invention is adopted as an affinity filler, the AAV9 adeno-associated virus can be effectively captured and mildly eluted, the virus purification and recovery effects are effectively improved, and the nano-antibody coupled solid-phase carrier is suitable for high-purity recovery of the AAV9 adeno-associated virus.

The invention provides a specific T cell receptor targeting KRAS G12V mutant epitope peptide (such as an amino acid sequence as shown in SEQ ID NO: 2) and anti-tumor application of the specific T cell receptor. The specific T cell receptor is composed of two peptide chains alpha and beta and can be specifically combined with a VVGAVGVGK-HLA-A * 11: 01 compound. The invention also provides an antigen binding fragment of the specific T cell receptor, a nucleic acid sequence for coding the T cell receptor, a vector containing the nucleic acid sequence, an engineered cell for expressing the T cell receptor, a composition containing the T cell receptor and application thereof. In addition, the invention also provides a method for screening the KRAS G12V specific T cell receptor. The specific T cell receptor and the antigen binding fragment thereof provided by the invention can be used as an immune effect activator to stimulate the immune response of a body, so that the effect of resisting diseases such as tumors and the like is achieved.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The invention relates to the technical field of agricultural biology, in particular to a method for producing 25-hydroxyvitamin D3 by fusing P450 enzyme, a mutant thereof and a whole-cell catalyst. The fusion P450 enzyme VK1-CYP116B46 comprises a Vdh-K1 redox structure domain of the P450 enzyme and a redox structure domain of the CYP116B46, and the Vdh-K1 redox structure domain and the CYP116B46 redox structure domain are connected through a linker. And carrying out linker screening on the VK1-CYP116B46, so as to obtain the mutant. Whole cells are directly adopted as a catalyst, enzyme purification is not needed, glucose dehydrogenase is introduced, glucose serves as a substrate to regenerate the cofactor NAD (P) H, expensive cofactors are prevented from being added, the production cost is reduced, and industrial production is facilitated; compared with a multi-component P450 enzyme adopted in the prior art, the conversion rate of VD3 is greatly improved by fusing P450 enzyme conversion.

The invention relates to the field of gene therapy, in particular to an RBM25 gene epigenetics activation technology based on a CRISPR / dCas9-SunTag system and application of the RBM25 gene epigenetics activation technology in ischemic heart failure treatment, the RBM25 gene epigenetics activation technology comprises the following steps: (a) protein containing inactivated Cas9 (dCas9) fused with a plurality of GCN4 peptide repetitive sequences, the number of the GCN4 peptide repetitive sequences is 8-12, and the dCas9 contains D10A and H840A double mutations; (b) a protein containing fusion of an anti-GCN4 single-chain antibody fragment (scFv) and a TET1 catalytic structural domain; (c) at least one gRNA of a target RBM25 gene promoter region, wherein a target sequence of the gRNA is selected from a sequence as shown in SEQ ID NO: 1-3; and (d) a lipid nanoparticle (LNP) system for delivery of said (a), (b), and (c).

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

The invention belongs to the field of gene engineering, and relates to a DNA binding protein based on TraC effect protein, a fusion protein with a cytosine / adenine base editing function, an editing system and nucleic acid molecules or constructs for encoding the DNA binding protein and the fusion protein. The invention also relates to complexes and kits for gene editing comprising the fusion proteins of the invention or the nucleic acid molecules encoding them. The base editing tool disclosed by the invention can realize efficient, accurate and safe base editing in cells of various eukaryotes such as animals and plants. The unique characteristics of the base editing tool enrich the types of existing base editing tools, and the base editing tool has wide application prospects.

The invention provides recombinant VIII type humanized collagen and application thereof, and the recombinant VIII type humanized collagen is of a triple helix structure, has good cell adhesion activity, does not generate immunological rejection and anaphylactic reaction when being applied to a human body, is a brand new human body synthetic biological material, and has good application prospects.

The invention discloses a porcine epidemic diarrhea virus antigen fusion protein, a coding gene and a porcine epidemic diarrhea vaccine prepared from the porcine epidemic diarrhea virus antigen fusion protein. The method comprises the following steps: screening to obtain a homosensory sequence of the spike protein of the porcine epidemic diarrhea virus, and fusing the homosensory sequence with a monomeric porcine ferritin heavy chain subunit to obtain an antigen fusion protein; in order to improve the expression quantity or the titer of the antigen fusion protein, the obtained antigen fusion protein is subjected to sequence optimization and then subjected to single-site or multi-site mutation, and the expression quantity and the titer of the obtained mutant are remarkably improved. According to the invention, a recombinant protein is expressed by using a silkworm or AcMNPV-insect cell and other eukaryotic expression systems to obtain a self-assembled ferritin nanoparticle antigen for displaying an S protein antigen protein on the surface of a cage structure of porcine ferritin, and a vaccine prepared from the prepared nanoparticle antigen can induce a widely neutralized anti-porcine epidemic diarrhea virus antibody; the porcine epidemic diarrhea virus vaccine has the potential of becoming a universal porcine epidemic diarrhea virus vaccine with cross immune efficacy.

The present invention relates to a new class of molecules for selective clearance of antibodies and the uses thereof for treating antibody-mediated diseases and disorders.

The technology described herein relates to novel CRISPR / Cas systems and components thereof, vectors, proteins, fusion proteins, ribonucleoprotein complexes and methods of using the novel systems and components. The new system can be used in CRIS PRi applications and can be fused with any number of effector domain patterns, such as nuclease, base editor, leader editor, and the like, to conduct a variety of DNA modifications.

The invention features polypeptides that include an extracellular ActRIIA variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRIIA variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving low red blood cell levels, e.g., anemia or blood loss; fibrosis; or pulmonary hypertension.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

The present application relates to a method of producing a protein comprising an unnatural amino acid (UAA), the method comprising culturing a host cell, where the host cell is a eukaryotic cell, together with a nucleotide sequence encoding a first recoding tRNA or a first recoding tRNA, where the first recoding tRNA comprises an anticodon complementarily paired with a first codon, wherein the first codon is a rare codon; a nucleotide sequence encoding a first aminoacyl-tRNA synthetase or a first aminoacyl-tRNA synthetase, the first aminoacyl-tRNA synthetase being capable of loading a first recoding tRNA with a first non-natural amino acid.

The invention discloses a bacterial polypeptide Gfo and application thereof in preparation of rheumatoid arthritis diagnosis products, and belongs to the technical field of rheumatoid arthritis diagnosis. The amino acid sequence of the bacterial polypeptide Gfo is LNSHGFLPETE. A diagnostic product prepared from the bacterial polypeptide Gfo can effectively detect that the level of an anti-bacterial polypeptide Gfo antibody in a biological sample of a rheumatoid arthritis patient is obviously higher than that of healthy people and other rheumatoid immune diseases similar to rheumatoid arthritis. In addition, in CCP antibody and RF negative patients, the increase is still significant. Therefore, the antibacterial polypeptide Gfo antibody is an important biomarker of rheumatoid arthritis, and provides an effective new method for diagnosis of RA, especially diagnosis of serum-negative RA.

Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems and non-LTR retrotransposon elements.

The invention relates to the technical field of biological medicine, in particular to cat allergen fusion protein, an mRNA immune preparation and application of the cat allergen fusion protein and the mRNA immune preparation. The amino acid sequence of the cat allergen fusion protein disclosed by the invention is as shown in SEQ ID NO.11. The cat allergen fusion protein provided by the invention is a fusion protein obtained by fusing key segments with strong sensitization of Fel d2 and Fel d4 proteins with Fel d1 full-length protein, the fusion protein can simultaneously cover main sensitization epitopes of Fel d1, Fel d2 and Fel d4, and the sensitization effect of cat allergens can be more comprehensively blocked. According to the cat allergen fusion protein provided by the invention, an mRNA immune preparation can be rapidly designed and synthesized, the expression of the cat allergen fusion protein can be accurately controlled in poultry bodies, the immunoreaction is more durable, and the prepared IgY antibody can effectively block allergic protein in cat oral saliva.

The invention provides a fluorescent protein selection marker staygold-ynaMr gene and application thereof, and belongs to the technical field of biological engineering. The method comprises the following steps: replacing codons of L-isoleucine in nucleotide sequences of a fluorescent protein gene staygold and a gene ynaM by using a rare codon ATA to respectively obtain the fluorescent protein gene staygold after codon replacement and the gene ynaMr after codon replacement, and connecting the two segments of genes after codon replacement by using a flexible protein peptide, and the fluorescent protein selection marker staygold-ynaMr gene is obtained. Experiments prove that the gene can obviously improve the screening efficiency of L-isoleucine high-yield strains.

Provided by the present invention are a bispecific T-cell engager, recombinant oncolytic virus thereof, and use thereof. The present invention provides an αCD47 and αCD3 bispecific T-cell engager. The present invention also provides an isolated nucleic acid molecule that encodes said bispecific T-cell engager. The present invention also provides an expression framework of said bispecific T-cell engager BiTE. The present invention also provides a recombinant oncolytic virus, and said oncolytic virus is operably inserted with or contains the expression framework of said bispecific T-cell engager BiTE. In the present invention, the bispecific T-cell engager is combined with the oncolytic virus, and in comparison with pure gene therapy or virotherapy, the oncolytic virus significantly enhances the inhibition capability on malignant tumors.

The invention belongs to the technical field of biological medicine, and particularly relates to an RSV pre-fusion F protein mutant and application thereof. The RSV pre-fusion F protein mutant has better stability and higher expression quantity and / or immunogenicity, and can be used for preparing an RSV antibody, preventing RSV infection, preventing and / or treating diseases caused by RSV infection, detecting the existence or content of the RSV antibody in a sample, diagnosing RSV infection and diagnosing the diseases caused by RSV infection.

The present disclosure provides compositions and methods useful in the treatment of trinucleotide repeat disorders, including Huntington's disease and Friedreich's ataxia. The present disclosure also provides gRNAs designed to target the HTT or FXN genes. Complexes comprising a base editor and any of the gRNAs disclosed herein are also provided by the present disclosure. The present disclosure further provides polynucleotides, vectors, cells, compositions, and kits. Methods of treating Huntington's disease and Friedreich's ataxia are also provided herein.

The present disclosure provides, inter alia, a recombinant engineered deubiquitinase (DUB) and methods for treating or ameliorating an inherited ion channelopathy, such as long QT syndrome, Brugada syndrome, or cystic fibrosis, in a subject. Further provided are methods for screening mutations causing such inherited ion channelopathies for a trafficking-deficient mutation that is treatable by the recombinant engineered DUB disclosed herein.

The present disclosure provides, inter alia, a recombinant engineered deubiquitinase (DUB) and methods for treating or ameliorating an inherited ion channelopathy, such as long QT syndrome, Brugada syndrome, or cystic fibrosis, in a subject. Further provided are methods for screening mutations causing such inherited ion channelopathies for a trafficking-deficient mutation that is treatable by the recombinant engineered DUB disclosed herein.

The invention discloses a novel separated guide editor based on a Csy4 system and related protein. The invention belongs to the technical field of biology, and particularly relates to a novel separated guide editor based on a Csy4 system and related protein. The fusion protein is a protein obtained by fusing Csy4 nuclease of which the amino acid sequence is SEQ ID No: 1 to one end of RT protein, the Csy4 nuclease is fused to the N end or C end of the RT protein, and the amino acid sequence of the fusion protein is SEQ ID No: 2 or SEQ ID No: 3. The fusion of Csy4 improves the editing efficiency of separated guided editing, and compared with separated PE3max, the editing efficiency of 12 important agronomic trait targets of 11 genes of rice is greatly improved. The research lays a foundation for developing a Csy4-based separated guide editor with higher editing efficiency in the future.

The invention relates to a fusion protein, an immunogenic composition and a recombinant degenerate vaccine for preventing and treating infection of various pathogenic streptococci, as well as a molecular architecture design, application and the like. According to the invention, three immune antigens, namely an elongation factor Tu (Tuf), a molecular chaperone DnaK and an elongation factor G (fusA), are screened, and it is proved that fusion protein molecules of the three antigens can significantly inhibit tissue lesions caused by infection of different serotypes and different types of streptococci, have good immunogenicity, play roles in immune protection and effective prevention and treatment, and have good application prospects. The bacillus subtilis has the characteristics of broad-spectrum and high-efficiency prevention of streptococcus bacterial infection, and has a wide application prospect.