427results about "Transferrins" 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 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.

This invention discloses a milk protein containing composition comprising: at least one milk protein; at least a first protein; at least a second protein; and at least a linker comprising an amino acid sequence coded by nucleotide sequence which is at least 80% similar to sequences selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21

Disclosed herein is an anti-transferrin receptor antibody that specifically binds to the human transferrin receptor and the rhesus monkey transferrin receptor, comprising i) a humanized heavy chain variable domain derived from the heavy chain variable domain of SEQ ID NO:01, and ii) a humanized light chain variable domain derived from the light chain variable domain of SEQ ID NO:26, wherein the dissociation rate of the antibody for the human transferrin receptor is equal to or less than (i.e., at most) the dissociation rate of anti-transferrin receptor antibody 128.1 for the rhesus monkey transferrin receptor, wherein the dissociation rate is determined by surface plasmon resonance, and anti-transferrin receptor antibody 128.1 has a heavy chain variable domain of SEQ ID NO:64 and a light chain variable domain of SEQ ID NO:65.

The present letter invention provides an engineered AAV capsid in which at least one protein on the capsid is modified to include an n-mer motif that promotes transduction of the capsid into the central nervous system (CNS) by interaction with a transferrin receptor. Further embodiments provide a carrier system comprising one or more carriers encoding an AAV capsid and a method of delivering a cargo to a CNS. The methods comprise administering an AAV capsid according to embodiments described herein in vivo or in vitro, and the AVV capsid comprises one or more carrier molecules.

Aspects of the disclosure relate to methods of reducing expression or activity of DUX4 (e.g., DUX4 protein and / or mRNA) and / or methods of treating facioscapulohumeral muscular dystrophy (FSHD) in a subject. In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., an RNAi oligonucleotide such as an siRNA) covalently linked to an antibody (e.g., anti-TfRl antibody).

The present invention belongs to the field of biomedicine, and specifically relates to an antimicrobial peptide derived from lactoferrin and its application. The antimicrobial peptide derived from lactoferrin, whose amino acid sequence is shown in any one of SEQ ID NOs: 1 to 98, has a broad-spectrum antimicrobial effect, especially significant antibacterial effect against Pseudomonas putida, Rhodococcus erythropolis, Bacillus subtilis, Malassezia furfur, Cryptococcus neoformans, and Candida albicans, and has great application value.

The invention discloses an application of knockout of PEP4 and BAR1 genes in reduction of degradation of Kluyveromyces marxianus on lactoferrin. The invention provides application of inhibiting expression of PEP4 protein and BAR1 protein in any one of the following aspects: (A1) reducing degradation of Kluyveromyces marxianus on lactoferrin; and (A2) reducing the degradation of the fermentation supernatant of the kluyveromyces marxianus on lactoferrin. Experiments prove that after the encoding gene of the PEP4 protein and the encoding gene of the BAR1 protein are knocked out in yeast cells, the lactoferrin degradation amount can be reduced, the complete protein amount is remarkably increased, and the method has important significance on increasing the secretory expression yield of the lactoferrin in kluyveromyces marxianus.

The invention relates to the technical field of antibacterial peptides, and discloses a preparation method and application of a multi-segment fused antibacterial peptide fusion protein. The antibacterial peptide fusion protein is obtained by introducing OST signal peptide and collagen and optimizing the connection sequence of the OST signal peptide, the collagen, bovine lactoferrin peptide LFcinB, bovine lactoferrin N-leaf small peptide LFcin and bovine lactoferrin N-leaf derived peptide Lf. The antibacterial peptide fusion protein can simultaneously contain three segments of bovine lactoferrin active peptides, namely LFcinB, LFcin and Lf, and the yield of the fusion peptide is maximized. Experiments prove that the fermentation yield of the fusion protein comprising the OST signal peptide, the collagen, the bovine lactoferrin peptide LFcinB, the bovine lactoferrin N-leaf small peptide LFcin and the bovine lactoferrin N-leaf derived peptide Lf which are sequentially connected from the N terminal to the C terminal can reach 600mg / L.

The invention discloses a method for preparing high-purity lysozyme and ovotransferrin through combined ion exchange chromatography, and belongs to the technical field of protein separation and purification and functional food. The lysozyme with the purity of 95.57% and the ovotransferrin with the purity of 97.89% are obtained through separation by combining cation exchange resin with anion exchange filler. Wherein the ovotransferrin has good oxidation resistance, has a relatively high inhibition rate on the growth of pseudomonas fluorescens, and does not lose the biological function in an acid environment, so that a basis is provided for improving the additional value of the egg white and developing antibacterial and anti-inflammatory functional foods.

The invention relates to a preparation method and application of recombinant canine lactoferrin and peptide thereof, aiming at codon preference of host cells, canine lactoferrin genes are optimized, the full length of canine lactoferrin and the lactoferrin peptide are successfully expressed by virtue of an escherichia coli expression system, and the recombinant canine lactoferrin and the peptide thereof are identified by virtue of a minimum inhibitory concentration experiment. It is proved that the canine lactoferrin and the peptide thereof have the inhibiting capacity on pathogenic bacteria such as staphylococcus aureus, salmonella typhimurium and staphylococcus pseudointermedius, and the antibacterial activity MIC of the canine lactoferrin on the staphylococcus aureus, the salmonella typhimurium and the staphylococcus pseudointermedius is 1.5 mg / mL; the antibacterial activity MIC of the dog lactoferrin peptide to staphylococcus aureus is equal to 0.75 mg / mL, and the dog lactoferrin peptide shows high antibacterial ability.

Herein is reported an anti-transferrin receptor antibody that specifically binds to human transferrin receptor and cynomolgus transferrin receptor, which comprises i) a humanized heavy chain variable domain derived from the heavy chain variable domain of SEQ ID NO: 01, and ii) a humanized light chain variable domain derived from the light chain variable domain of SEQ ID NO: 26, wherein the antibody has an off-rate for the human transferrin receptor that is equal to or less than (i.e. at most) the off-rate of the anti-transferrin receptor antibody 128.1 for the cynomolgus transferrin receptor, whereby the off-rates are determined by surface plasmon resonance, and whereby the anti-transferrin receptor antibody 128.1 has a heavy chain variable domain of SEQ ID NO: 64 and a light chain variable domain of SEQ ID NO: 65.

The invention provides a safrole hapten and application of the safrole hapten in detection of safrole through immunoassay. The structure of the safrole hapten is shown in the specification. The two safrole haptens provided by the invention have spacer arms with proper lengths, and after the safrole haptens are coupled with carrier protein, the haptens can be fully exposed, and recognition of the spacer arms can be avoided as much as possible. The safrole hapten is used for preparing an artificial antigen and an antibody, and the obtained safrole monoclonal antibody is high in titer, strong in specificity and high in affinity. An immunoassay method constructed on the basis of the safrole artificial antigen and antibody has high specificity and sensitivity, the lowest detection limit LOD is 0.09 ng / mL, the half inhibitory concentration IC50 is 2.05 ng / mL, the quantitative detection range is 0.28-14.89 ng / mL, no cross reaction exists on safrole analogues, and rapid qualitative and quantitative detection can be conducted on safrole in a sample.

The invention belongs to the field of biological medicines, and discloses an application of a protein polymer in preparation of a medicine for treating Alzheimer's disease, a production process of the protein polymer comprises the following steps: S1) using ultraviolet irradiation to stimulate mesenchymal stem cells and culturing; and S2) splitting the mesenchymal stem cells, separating and purifying to obtain the protein polymer. According to the present invention, the mesenchymal stem cells are stimulated to express the protein with the nerve repair function through the ultraviolet irradiation stress mode, and the protein polymer is obtained through further separation and purification, such that the protein polymer can be adapted to diversified application modes, can improve the abnormal conditions of the Alzheimer's disease related biomarkers, and can provide the significant treatment effect on the Alzheimer's disease.

The invention discloses a method for preparing low-bitterness micromolecular bovine colostrum protein peptide powder by adopting a multi-stage membrane separation and enzyme membrane coupling combined technology, and belongs to the technical field of food processing. The preparation method comprises the following steps: firstly, dividing a colostrum component into components to be hydrolyzed by adopting a multi-stage membrane separation technology, namely casein intercepted by ceramic membrane microfiltration and lactoglobulin and lactalbumin filtered by an ultrafiltration membrane, and non-hydrolytic components, namely immune globulin and lactoferrin; the preparation method comprises the following steps: firstly, separating bovine coloctrum, then deeply hydrolyzing the separated lactoglobulin, milky white and casein flocculate with the molecular weight of less than 50kDa by adopting an enzyme membrane coupling technology, mixing with unhydrolyzed immunoglobulin and lactoferrin, and freeze-drying, so that the peptide content in the treated bovine coloctrum is more than 40%, the peptide content of 200-1000Da is more than 30%, the peptide content of 200-1000Da is more than 30%, and the peptide content of 200-1000Da is more than 30%. The preparation method is simple, the preparation dispersion time is within 10 s, no obvious bitter taste exists, the retention rate of immune globulin in bovine coloctrum reaches 90% or above, and the preparation method is suitable for large-scale industrial popularization.

The invention discloses a preparation method and application of an ovotransferrin oligomer with an immunomodulatory effect, and a function enhanced nano oligomer is constructed through an enzymatic crosslinking and dynamic hot pressing synergistic treatment technology. The preparation method comprises the following specific steps: preparing an ovotransferrin solution, adjusting the pH value to 1.5-2.0, carrying out high-pressure homogenization and double-frequency ultrasonic treatment after pre-denaturation, adding TG enzyme to catalyze, crosslink and induce controllable aggregation, and finally freeze-drying to obtain oligomer powder, the oligomer is of a nano-scale spherical structure, the particle size is 50-200nm, the solubility is good, and the immunoregulation function is remarkably enhanced. Comprising the steps of promoting dendritic cells to secrete immune factors, prolonging the survival time of nematodes under bacterial infection and improving the immune function of immunosuppressive mice. The method disclosed by the invention is simple in process, green and environment-friendly, suitable for the fields of functional health-care products, pharmaceutical preparations, formula foods with special medical purposes and the like, and wide in application prospect.

The invention discloses a method for screening high-yield recombinant human lactoferrin through nucleic acid aptamer-assisted mutagenesis of a trichoderma reesei strain and application, and belongs to the technical field of microorganisms. The nucleic acid aptamer Lac-6a-FAM-BHQ1 capable of changing the fluorescence intensity according to the content of lactoferrin is constructed on the basis of the aptamer Lac-6a, and the nucleic acid aptamer can be used for rapidly selecting a mutant strain for producing high-titer recombinant human lactoferrin. The ARTP mutagenesis technology is combined with a nucleic acid aptamer auxiliary screening system, the mutant strain with the improved recombinant human lactoferrin yield is rapidly obtained from a large number of mutant strains, and the yield reaches 274.57 mg / L and is improved by 24.8% compared with that of an original strain. After the genes 111681 and 62716 are over-expressed in T. reesei, compared with a control strain, the yields of the recombinant human lactoferrin of the recombinant strain are respectively increased by 6.9% and 22.1%.

In the first aspect, the present disclosure provides a Lactoferrin polypeptide fragment, where the Lactoferrin polypeptide fragment has an amino acid sequence shown in SEQ ID NO: 1. In the second aspect, the present disclosure provides a preparation method of the Lactoferrin polypeptide fragment, including: protecting amino acids using a 9-fluorenylmethoxycarbonyl (Fmoc) protecting group, coupling the amino acids with a P-hydroxymethylphenoxymethyl polyethylene resin (HMP resin) in an order of cysteine, alanine, leucine, cysteine, glutamate, threonine, asparagine, aspartate, asparagine, phenylalanine, leucine, leucine, asparagine, and lysine, and separating the HMP resin to obtain a target Lactoferrin polypeptide fragment. In the third aspect, the present disclosure further provides an anti-Lactoferrin antibody prepared using the Lactoferrin polypeptide fragment, and use of the Lactoferrin polypeptide fragment in preparation of an anti-Lactoferrin flow cytometric antibody and in preparation of a Lactoferrin detection product.

The invention is applicable to the technical field of molecular biology, and provides a polypeptide specifically bound with a transferrin receptor, the polypeptide comprises a general formula of H1-H2-E1-E2-H3-H4-E3, and H1, H2, H3 and H4 independently comprise an alpha helical domain; the E1, the E2 and the E3 respectively and independently comprise a beta folding structural domain; when the polypeptide is combined with the hTfR1, transferrin is allowed to be combined to the hTfR1; the polypeptides are capable of binding and delivering oligonucleotides. The invention also provides a recombinant nucleic acid encoding the polypeptide, an expression vector comprising the recombinant nucleic acid, a recombinant host cell comprising the polypeptide, the nucleic acid and / or the expression vector, a conjugate of the polypeptide and oligonucleotide, and a corresponding pharmaceutical composition. The polypeptide disclosed by the invention can be highly specifically combined with hTfR1, so that accurate delivery of oligonucleotide is realized, and a practical basis is provided for treating diseases related to gene mutation.

The invention belongs to the field of food nutrition and functional factors, and particularly relates to a method for preparing ovotransferrin hydrolysate with high immunocompetence based on an adult gastrointestinal simulated digestion system. According to the method, ovotransferrin is treated through the stomach and intestine of a simulated adult, OVT hydrolysate is prepared, and the OVT hydrolysate contains HTEGSTT, TTSY and / or RTAGWVIPMG. The invention finds that the immunomodulatory activity of OVT is enhanced after gastrointestinal digestion and hydrolysis, the OVT is more easily hydrolyzed in simulated adult digestive juice than in infant digestive juice, and a contrast experiment shows that the nutrition intervention of OVT adult and infant simulated digestion products can promote the generation of short-chain fatty acids such as acetic acid, propionic acid and butyric acid; the swelling injury caused by inflammation to small intestine mucous membrane tissues is effectively relieved, so that the intestinal barrier immune function is obviously improved, and the OIA shows higher intestinal immune activity than the OIB.

The invention belongs to the field of biological medicines, and discloses an application of a protein polymer in preparation of a medicine for treating spinal cerebellar ataxia disease, a production process of the protein polymer comprises the following steps: S1) using ultraviolet irradiation to stimulate mesenchymal stem cells and culturing; and S2) splitting the mesenchymal stem cells, separating and purifying to obtain the protein polymer. An ultraviolet irradiation stress mode is adopted, mesenchymal stem cells are stimulated to express protein with a neural repair function, the protein polymer is obtained through further separation and purification, the cell gene expression pathway is regulated, the cell stress state is relieved, the cells are promoted to recover normal forms and functions, meanwhile, the preparation mode is relatively simple, and the preparation method is suitable for large-scale production. And quality and yield monitoring is facilitated, and the method can be adapted to diversified application modes.

The invention relates to the technical field of high-activity immune globulin liquid extraction, in particular to a preparation method for extracting high-activity immune globulin liquid from bovine colostrum. The invention discloses a preparation method for extracting high-activity immune globulin liquid from bovine coloctrum, which comprises the following steps: performing primary separation, secondary separation, filtration, ultrafiltration concentration and sterilization on degreased bovine coloctrum to obtain the high-activity immune globulin liquid, the primary separation comprises the following steps: adjusting the pH value of the defatted bovine colostrum to 4.6-4.7, and sieving to remove casein, so as to obtain whey; and the secondary separation comprises the following steps: adjusting the pH value of the whey to 3.8-4.0, uniformly mixing, and sieving to remove denatured protein to obtain an immunoglobulin liquid. The high-activity immune globulin liquid containing IgG, IgA, IgM, lactoferrin, lactoperoxidase, IGF-beta, lysozyme, lactose and protein, which is prepared by adopting the method disclosed by the invention, can be used for effectively improving the immunity of a human body.

The invention discloses pichia pastoris for efficiently synthesizing lactoferrin as well as a construction method and application of the pichia pastoris, and belongs to the technical field of biosynthesis. The pichia pastoris for efficiently synthesizing the lactoferrin expresses at least one of KAR2, PDI1 and ERO1 in molecular chaperones in a host in an enhanced manner and carries an optimized secretory signal peptide, and the secretory signal peptide is obtained by replacing a leading peptide of alpha-factor with any signal peptide in LacZ, PelB, FLO and alpha-factor. The yield of LF can be effectively increased by enhancing expression of at least one of KAR2, PDI1 and ERO1 molecular chaperones in molecular chaperones in a host; when the lactoferrin expression cassette is integrated into the recombinant pichia pastoris X-33 genome and the copy number is increased to 2-6, the LF yield can be further increased, and when the copy number is 4, the LF yield reaches a peak value.

The invention provides an analgin hapten, a preparation method thereof, an artificial antigen, an antibody and application. The structures of the analgin haptens are as shown in a formula (I) or a formula (II), the two analgin haptens provided by the invention have spacer arms with proper lengths, and after the two analgin haptens are coupled with protein, the haptens can be fully exposed to an immune system, the spacer arms can be prevented from being recognized as much as possible, and a better antibody is generated to recognize analgin. The analgin hapten is used for preparing artificial antigen and antibody, the obtained analgin monoclonal antibody has high titer and strong specificity, an immunoassay method constructed based on the analgin monoclonal antibody has high specificity and sensitivity, analgin in a sample can be rapidly, qualitatively and quantitatively detected, the operation is simple and convenient, and the detection result is accurate and reliable.

Described herein are compositions and methods for selective depletion of target molecules using a recyclable CDP-receptor-binding mediated complex to elicit endocytosis and cellular degradation of the target. Exemplary compositions containing a peptide, such as a CDP peptide, that bind a transferrin receptor can be linked to a peptide that binds a target molecule. Such compositions can be used to selectively recruit the target molecule to endosomes via transferrin receptor-mediated endocytosis of the composition and the bound target molecule. Once inside the endosome, the acidic pH can lead to release of the target molecule from the composition due to pH-dependent binding of the composition for the target molecule, and the transferrin receptor portion is recycled back to the cell surface for “reloading”. The target molecule can then be trafficked into lysosomes wherein it is degraded.

The invention discloses a method for rapidly and efficiently extracting ovotransferrin in egg white, which comprises the following steps: (1) pre-treating egg white, namely treating egg white liquid through an ultrasonic composite high-voltage pulse electric field, so that the thick protein is thinned, the viscosity is further reduced, molecules are dispersed, the egg white liquid is prevented from being diluted by adding water in the subsequent process, and the production efficiency is favorably improved; (2) removal of ovomucin and ovalbumin: removing the ovomucin and ovalbumin by an isoelectric precipitation method combined with a PEG precipitation method; (3) preparation of ovotransferrin; (4) separating an ovotransferrin crude product; and (5) purifying the ovotransferrin crude product. According to the method disclosed by the invention, high-yield and high-purity ovotransferrin is rapidly and efficiently prepared, and the method is simple, relatively low in cost and suitable for large-scale industrialization.

The present invention relates to novel enzyme nanoparticles capable of converting methane into methanol, in which key active sites of methane-oxidizing bacteria are fused with each other and expressed on a protein that can be self-assembled in cells to form nanoparticles, and specifically to enzyme nanoparticles including a protein having methane monooxygenase (MMO) activity and active sites of the methane oxidase, a method for production thereof, a recombinant microorganism into which a nucleic acid encoding the protein and the active site of the methane oxidase is introduced, and immobilized enzyme nanoparticles including the enzyme nanoparticles loaded on a carrier.

The invention discloses an enhancer regulatory element for transcriptional regulation expression of a human LTF gene and application of the enhancer regulatory element. The sequence of the regulatory element is SEQ ID No.1. Experiments prove that the human specific regulatory element can significantly activate report gene expression (improved by 14.93 times) in a bovine mammary epithelial cell line (MACT), the limitation of dependence on species conservative elements in the prior art is broken through, and an expression system designed based on the element can realize human level LTF high-efficiency expression. And a brand new tool is provided for development of mammary gland bioreactors and functional dairy products.

The present invention relates to a ferritin nanocage fused with PD-L1-binding peptide 1 and a use thereof as an anticancer immunotherapy agent. Prepared in the present invention were nanocages that are formed by fusing a human ferritin monomer with a peptide 1 (PD-L1pep1: CLQKTPKQC) binding to the immune checkpoint receptor PD-L1 overexpressed in many cancers such as breast cancer, colorectal cancer, renal cancer, glioblastoma, etc. and which display 24 Pd-L1prep1. The nanocages of the present invention effectively target colorectal cancer tissues to exhibit an anticancer effect. When loading the anticancer agent doxorubicin thereinto, the nanocages showed higher anticancer effects than the same dose of PD-L1 antibody. Accordingly, the nanocages are expected as a next-generation drug that surmounts the limitation of immune checkpoint blocking therapy using antibodies.

The present invention relates to a method for producing a recombinant protein by using a PDI derived from Trichoderma sp. strain. A variant yeast comprising a gene that encodes a PDI derived from Trichoderma sp. (the genus Trichoderma) strain, of the present invention, highly expresses a target protein, and thus is used to produce a target recombinant protein at a high yield.

The disclosure provides conjugates comprising a targeting moiety, e.g., an antibody, Fab fragment or single chain variable fragment (ScFv), and a lipid nanoparticle (LNP) encapsulating a therapeutic agent (i.e., payload), wherein the targeting moiety, e.g., antibody, Fab fragment or the ScFv, is conjugated to the lipid nanoparticle through a linker, and wherein the linker comprises an enzyme recognition sequence such as a sortase recognition motif or a lipoic acid acceptor peptide. The disclosure further provides methods of preparing such conjugates.