10729results about "Fusion polypeptide" patented technology

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 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 recombinant human III-type collagen which is of a triple-helix structure and assembled into collagenous fibers and application of the recombinant human III-type collagen, and belongs to the technical field of bioengineering. Collagen fragments capable of forming a triple helix structure are screened out through a bioinformatics algorithm, the fragments are connected in series, a key C-terminal structural domain and a specific amino acid sequence are combined, and formation of a stable triple helix advanced structure and assembly of collagenous fibers are effectively promoted. The recombinant human III type collagen is efficiently expressed through a eukaryotic expression system, and shows excellent stability, low immunogenicity and good biocompatibility. Experimental results show that the prepared recombinant human III-type collagen not only has a natural triple helix structure, but also can be further assembled into macromolecular collagen fibers, is suitable for multiple fields such as medical beauty, bioengineering and tissue repair, and has wide application prospects and market values.

The invention discloses a recombinant humanized XVII type collagen as well as an expression vector and a genetically engineered bacterium thereof. Four functional fragments with high activity are obtained through screening, one of the fragments is optimized and then combined according to a certain sequence to obtain recombinant humanized XVII type collagen JYC1703, or one of the fragments is optimized and then combined according to a certain sequence, and GPP sequences are fused at an amino terminal and a carboxyl terminal respectively to obtain recombinant humanized XVII type collagen JYC1701 and JYC1702, and the recombinant humanized XVII type collagen JYC1701 and JYC1702 are combined according to a certain sequence to obtain the recombinant humanized XVII type collagen JYC1701 and JYC1702. After codon optimization, amplifying and cloning into an expression vector, transforming into pichia pastoris competent cells after enzyme digestion linearization, and screening high-copy recombinants through G418 resistance gradient, so as to obtain pichia pastoris genetically engineered bacteria for expressing recombinant humanized XVII type collagen. The recombinant humanized XVII type collagen JYC1701, JYC1702 and JYC1703 disclosed by the invention show excellent functions of promoting cell adhesion, cell proliferation and cell migration, and are suitable for preparing products such as skin care products or medical instruments and the like.

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 invention discloses a recombinant herpes zoster vaccine as well as a preparation method and application thereof, and particularly relates to the technical field of biological medicines. The recombinant herpes zoster vaccine comprises a recombinant herpes zoster vaccine fusion protein purified product HN101 and a liposome mixture HA201, and the recombinant herpes zoster fusion protein gE-gD is constructed by recombining reconstructed gE protein and reconstructed gD protein. The gE-gD recombinant herpes zoster fusion protein is obtained by reconstructing gE protein of varicella-herpes zoster virus and gD protein of HSV through a gene recombination technology and then recombining the gE protein and the gD protein. After the gE-gD recombinant herpes zoster fusion protein is combined with a liposome mixture HA201, stronger immune response can be induced, the antibody titer and cellular immunity are improved, the vaccine effect is enhanced, and meanwhile, the potential infection risk is avoided.

The present invention provides the method for the separation of at least more than two Low molecular weight (LMWs) impurities present in the protein mixture comprising fusion protein CTL4-IgG1 by using Capillary Electrophoresis-Sodium dodecyl sulfate (CE-SDS) wherein the loading amount of protein mixture is more than 270 μg. The invention further provides a ratio of protein to sodium dodecyl sulfate is 2.7:1 or higher.

The invention discloses a fusion enzyme capable of efficiently degrading PET (polyethylene terephthalate) plastic and application of the fusion enzyme. The invention provides a recombinant fusion enzyme. The recombinant fusion enzyme comprises a mutant KL-MHETase of thermophilic carboxylesterase Est30 and a PET (Polyethylene Terephthalate) degrading enzyme FAST-PETase, the amino acid sequence of the mutant KL-MHETase of the thermophilic carboxylesterase Est30 is as shown in SEQ ID NO. 3; the amino acid sequence of the FAST-PETase is as shown in the 284th to 546th amino acids of SEQ ID NO.1 (Sequence Identifier Number 1). The fusion enzyme is used as a biocatalyst, the activity of catalyzing hydrolysis of MHET at 50 DEG C is 52.6 times that of FAST-PETase, and the fusion enzyme has high enzyme activity and thermal stability. PET degradation is catalyzed at the temperature of 50 DEG C, the conversion rate of PET is 90% after 48 hours of reaction, and meanwhile, the TPA content in the product is close to 100%.

The invention discloses a genetically engineered algae capable of resisting aquatic pathogenic bacteria as well as a construction method and application thereof, and is characterized in that the genetically engineered algae is phaeodactylum tricornutum into which cell wall energizing plasmids pPha-T1-J48054-eGFP-Linker-Q4 or pPha-T1-J48054-eGFP-Linker-Q6 are introduced, and the preparation method of the genetically engineered algae comprises the following steps: taking genome DNA of the phaeodactylum tricornutum as a template; the method comprises the following steps: constructing a directional expression plasmid pPha-T1-J48054-eGFP by amplifying a Phatr3J48054 coding sequence, inserting Q4 and Q6 coding sequences into the downstream of the eGFP of a directional expression vector, constructing a cell wall energizing plasmid, electrically transforming the cell wall energizing plasmid into phaeodactylum tricornutum, coating an f / 2 plate culture medium with transformed phaeodactylum tricornutum cells for culturing, screening positive algae strains, and screening the positive algae strains. The feed additive has the advantage of inhibiting or killing aquatic pathogenic bacteria.

This invention provides a tetrahedral antibody comprising a first, second, third, fourth, fifth, and sixth domain, wherein each of the first and second domains are an Fc domain of an IgG antibody comprising S239D and I332E mutations on both the first polypeptide chain and second polypeptide chain of the domain; the third domain and fourth domains are each a Fab domain comprising the V region of a Fab domain of FMC59 or a variant thereof with at least 95% identity to said V region; and the fifth and sixth domains are each a Fab domain comprising the V region of a Fab domain of Rituximab or a variant thereof with at least 95% identity to said V region.

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 disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins further comprise a nuclear localization sequence (NLS), and / or an inhibitor of base repair, such as, a nuclease dead inosine specific nuclease (dISN).

The invention relates to a drug delivery carrier based on extracellular vesicles and application thereof.The drug delivery carrier contains extracellular vesicle scaffold protein and recombinant membrane fusion protein, the recombinant membrane fusion protein comprises a first fragment and a second fragment, the amino acid sequence of the first fragment is shown as SEQ ID NO: 5, and the amino acid sequence of the second fragment is shown as SEQ ID NO: 6; the second fragment has n amino acids, the sequence of the second fragment is the sequence of the first n amino acids at the N end of the amino acid sequence as shown in SEQ ID NO: 7, and n is an integer between 50 and 200. According to the drug delivery carrier disclosed by the invention, the efficiency of releasing drug active molecules before reaching lysosome is remarkably improved, and the drug effect of extracellular vesicle drugs can be improved.

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 present invention relates to strategies for combining elements of non-ribosomal peptide synthase (NRPS) and polyketide synthase (PKS) into functional enzymes to promote the production of peptides and polyketide of any sequence. The present invention is based on the use of conserved sequence motifs within the T domain (or T domain-like) gene of the NRPS / PKS, which is used according to the invention as fusion sites for the production of new (and artificial) NRPS / PKS enzymes that can produce any peptide or polyketones of interest. The present invention provides artificial NRPS / PKS of the invention, methods and means for generating them, and nucleic acid libraries encoding various modules useful for designing NRPS / PKS for any peptide sequence of interest.

The invention belongs to the field of animal vaccines, and particularly relates to a multi-epitope fusion protein aiming at multi-serotype laisseria parasuis antigen and application. The applicant carries out proteomics analysis on four clinical isolated strains of serotypes 4, 5 and 13 of the parasuis leather serotype 4, 5 and 13 with high toxicity and good immunogenicity, and eight antigen proteins are screened out of the four clinical isolated strains of the serotypes 4, 5 and 13 of the parasuis leather serotype 4, 5 and 13. And further analyzing the screened eight antigen proteins to finally obtain the antigen multi-epitope fusion protein with immunogenicity capable of recognizing three serotypes. When the fusion protein is used as a vaccine, the protection rate of clinically separated piglets infected with a serum type 4 strain HB04, a serum type 5 strain SJZ05 and a serum type 13 strain GD20 reaches 100%.

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 discloses a MAGE-A10 specific TCR (T cell receptor) and an application thereof. The invention provides a TCR (T cell receptor) which has high antigen sensitivity and can remarkably kill target cells, and also provides nucleic acid for coding the TCR, a carrier comprising the nucleic acid, a cell, a pharmaceutical composition and application of the TCR in preparation of the pharmaceutical composition for treating tumors and screening of antigen detection products.

The invention discloses an optimized NlovFz2-omega RNA (Ribonucleic Acid) editing system, the optimal NlovFz2 system enNlovFz2 is obtained by modifying NlovFz2 protein and an omega RNA skeleton, and on the basis of remarkably improving the editing efficiency compared with a parent NlovFz2 system, the NlovFz2 mutant protein and T5 exonuclease are fused to obtain an enNlovFz2-T5 system with higher editing efficiency. The method has important significance and value for promoting wide application of a gene editing technology in the aspects of functional mechanism research and clinical treatment.

The present invention relates to T lymphocytes targeting CLD18A2 and a preparation method and application thereof. The inventors have successfully found a target gene CLD18A2 suitable for developing CAR T cells from a number of tumor-related genes for the first time, and successfully prepared CAR T cells targeting CLD18A2, thereby providing a new treatment method for pancreatic cancer, gastric cancer and other tumors.

The invention discloses a fusion protein and application thereof. Fusion expression is carried out on R ring binding domains from different species sources and a single gene base editor, and it is found that compared with a base editor before fusion, the base editing efficiency of the obtained fusion protein is improved, and a base editing window is widened. According to the method, the R-ring binding structure domain is fused with the single-gene base editor, so that the base editing efficiency can be improved, and an editing window can be adjusted, so that the method can be suitable for more base editing scenes. The method is beneficial to popularization and application of a single-gene editing technology, and has wide application prospects in prevention and / or treatment of diseases and construction of animal models or plant varieties.

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.