3701results about "Peptidases" patented technology

The present disclosure provides proteins useful for preventing, treating, inhibiting and / or eliminating infestation and infection of plants caused by various phytopathogenic pests, as well as formulations comprising such proteins, polynucleotides encoding such proteins, organisms expressing such proteins, and methods for preparing such proteins. And methods of using such proteins, formulations, polynucleotides, and organisms in agricultural and other effort areas.

A dual-targeting siRNA agent, comprising two different siRNAs targeting two different genes or pharmaceutically acceptable salts thereof, the two different siRNAs or salts thereof being linked to each other by means of a pharmaceutically acceptable ligand, the siRNAs being dsRNAs consisting of sense strands and antisense strands, and the two different genes being two selected from angiotensinogen (AGT), proprotein convertase subtilisin / kexin type 9 (PCSK9) and human angiopoietin-like protein 3 (ANGPTL3). Also provided is the use of the dual-targeting siRNA agent in preparing a drug for preventing or treating diseases related to hypertension or / and lipid imbalance. The dual-targeting siRNA agent can simultaneously and effectively inhibit the expressions of the two target genes in vivo, and has the advantages of no mutual antagonism, high activity and high safety. Further provided are siRNAs of genes corresponding to the dual-targeting siRNA agent and the use thereof for preventing or treating diseases related to hypertension or / and lipid imbalance.

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 invention discloses a pharmaceutical composition comprising a circular RNA and a drug delivery carrier. Compared with traditional linear 1 * siRNA and annular 1 * siRNA, the number of repeated series connection of positive-sense strands is increased to include but not limited to two or more, it is accidentally found that the silence effect is remarkably enhanced, the expression level of the PCSK9 gene can be remarkably reduced, and degradation of mRNA of PCSK9 protein is mediated. The nano-particles are used for delivering oligonucleotide, so that the stability is improved, the immunogenicity is reduced, the effects of lowering cholesterol, reducing aortic plaque load and resisting atherosclerosis are improved, and the nano-particles are safe and free of obvious liver and kidney toxicity and have a wide application prospect in the aspect of preparing medicines for treating hypercholesterolemia and coronary heart disease.

The present disclosure provides a preparation method of a yak hide-derived oligopeptide ferrous chelate with a high antioxidant activity. The preparation method includes preparing a yak hide-derived oligomeric collagen peptide and subjecting the yak hide-derived oligomeric collagen peptide as a protein source to chelation with an iron source in water. A pretreated yak hide is subjected to enzymatic hydrolysis under a pH value of 7 at 50° C. for 4 h with an amount of an enzyme added at 2% to obtain a yak skin-derived collagen with a molecular weight of less than 2 kDa; the chelation is conducted in a peptide-to-iron mass ratio of 1:1 to 5:1 with a peptide concentration of 1% to 5% at 30° C. to 70° C. for 20 min to 60 min under a pH value of 3 to 8; and an iron chelating capacity is 42.72 mg / g under optimal preparation conditions.

Relating to the technical field of gene therapy, provided is an siRNA molecule for inhibiting PCSK9 expression, and use thereof. Particularly, an siRNA molecule for inhibiting PCSK9 expression (comprising a sense strand and an anti-sense strand that are complementary to form a double-stranded region) and a pharmaceutical composition comprising the same are disclosed. The siRNA molecule has a high silencing efficiency and a long-lasting silencing effect for PCSK9 gene, and is useful in the manufacture of products for inhibiting PCSK9 protein expression, products for reducing the concentration of low-density lipoprotein or low-density lipoprotein cholesterol in serum; and products for relieving the symptoms of PCSK9 gene-mediated diseases.

The invention provides annular multi-tandem PCSK9 siRNA, which comprises at least one positive-sense strand sequence and at least one spacer sequence. The sense strand of the cyclic siRNA is derived from an engineered parent DNA template containing all essential sequences, comprising in the following order a first cyclization element, optionally at least one first restriction enzyme recognition sequence, at least one target sequence, optionally at least one second restriction enzyme recognition sequence, and a second cyclization element. The annular multi-tandem RNA positive-sense strand can combine and deliver a plurality of antisense strand RNAs, and the combination of the positive-sense strand and the antisense strand is increased while the stability advantage of the annular RNA is utilized.

This invention provides a tetrahedral antibody comprising a first, second, third, and fourth domain, wherein the first and second domains are Fab or Fc domains; wherein each of the first and second domains comprise a first polypeptide chain comprising a first N-terminus of the domain, and a second polypeptide chain comprising a second N-terminus of the domain; wherein the first N-terminus of the first domain and the first N-terminus of the second domain are joined to each other by a non-peptidyl linkage, which can be a covalent linkage or a non-covalent linkage between first and second dimerizing polypeptides attached to the first N-termini of the first and second domains, respectively; and wherein the third and fourth domains are attached at their respective C-termini to the second N-termini of the first and second domains, respectively, or the N-termini of the first and second dimerizing polypeptides.

The invention relates to the field of gene engineering and enzyme engineering, in particular to an acid protease mutant with improved stability and a product and application thereof. In particular to an acid protease mutant IAIC6M with improved heat resistance and a coding gene thereof. A mutant IAIC6M is obtained by performing D86I, G168A, Q185I and Q339C mutation on an iaic6 sequence as shown in an amino acid sequence SEQ ID NO.1, and compared with IAIC, the mutant can still maintain more than 60% of enzyme activity at 75 DEG C for 3 minutes, while the IAIC can only maintain 20% of enzyme activity at 75 DEG C for 3 minutes; the acid protease mutant IAIC6M disclosed by the invention has the following properties: the optimum pH is 3.0, and the acid protease mutant IAIC6M still has higher enzyme activity under a high-temperature condition and has wide application value in the aspects of industry, food, medicine and the like.

A nucleic acid molecule comprising: i) a first nucleic acid comprising a double stranded inhibitory ribonucleic acid (RNA) molecule comprising a sense and an antisense strand designed with reference to a nucleotide sequence comprising a cardiovascular disease associated gene to be silenced and wherein said cardiovascular gene is proprotein convertase subtilisin kexin 9 (PCSK9) there is provided a single stranded deoxyribonucleic acid (DNA) molecule conjugated to the 5’ end of said sense strand; and ii) a second nucleic acid comprising a double stranded inhibitory ribonucleic acid (RNA) molecule comprising a sense and an antisense strand designed with reference to a different cardiovascular disease associated gene to be silenced wherein said cardiovascular gene is lipoprotein (a) (Lp(a)) and wherein there is provided a single stranded deoxyribonucleic acid (DNA) molecule conjugated to the 5’ end of said sense strand wherein the single stranded deoxyribonucleic acid (DNA) molecule is substantially complementary to the single stranded deoxyribonucleic acid (DNA) molecule set forth in i) above and anneals by complementary base pairing to form a double stranded DNA linker that links the first and second double stranded inhibitory ribonucleic acid (RNA) molecules.

The embodiment of the invention is to conformationally constrain neutralizing B cell epitopes of CoV-2, CoV-n B cell epitopes of the open reading frame proteins, including the membrane S protein, constrained by protein scaffolds, including camelid VHH nanobody in order to elicit neutralizing and blocking antibodies against viral infection. B cell epitopes are molecularly evolved by ribosome display to preempt emerging viral B cell epitopes. Moreover, CTL epitopes are designed from the open reading frame protein for eliciting cell mediated viral protection. Furthermore, mRNA vaccines are prepared for eliciting protective immunity and prevent cytokine storms.

The present invention relates to a macrophage, genetically engineered to overexpress Interleukin-10 (IL-10) or IL-10 in combination with Matrix Metallopeptidase 9 (MMP9). Such a macrophage may be for use in treatment of liver cirrhosis in a subject. In particular, the subject may be treated after having undergone a first hepatic decompensation event which required the subject's hospitalisation. The subject may have undergone a subsequent decompensation event prior to treatment.

Disclosed are, inter alia, double stranded RNAi (dsRNAi) agents inhibiting expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), for example, human HMGCR, compositions including the same, and methods of treatment using the same.

Disclosed in the present invention are a dissociation agent and a detection kit for thyroid function detection. The dissociation agent comprises a protease and a reducing agent, and can effectively dissociate the bound forms of T3 and T4 in serum from binding proteins to form a free state. The dissociation agent and kit of the present invention are used for fluorescent immunochromatography detection, so that signal interference can be effectively reduced, and the sensitivity and accuracy of the detection can be improved.

Provided is a pharmaceutical composition, comprising a circular RNA and a drug delivery carrier. It is surprisingly found that compared with conventional linear 1 x siRNAs and circular 1 x siRNAs, increasing the number of tandem repeats in the sense strand to two or more significantly enhances the silencing effect, significantly reduces the expression level of the PCSK9 gene, and mediates the degradation of the PCSK9 protein mRNA. The use of nano-particles for delivering oligonucleotides features improved stability, reduced immunogenicity, improved cholesterol-lowering, aortic plaque load-reducing and anti-atherosclerotic effects, good safety, no significant liver and kidney toxicity, and therefore good prospects in preparing medicaments for treating hypercholesterolemia and a coronary heart disease.

The present invention discloses an interfering RNA for inhibiting PCSK9 gene and use thereof. The interfering RNA comprises a nucleotide sequence set forth in any one or two or more of SEQ ID NOs: 1-40, 73-96. The interfering RNA of the present invention can better target and silence hepatic PCSK9 mRNA, reduce the protein level of PCSK9, enhance LDL-C metabolism, and reduce serum cholesterol, providing a solid technical foundation for the development of siRNA medicaments for the prevention, treatment, and symptom alleviation of PCSK9 gene-mediated diseases.

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing enzymes or enzyme domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing enzymes or domains, are provided.

Provided herein are systems, compositions, and methods for generating immunogenic peptides or epitopes from tumor associated antigens (e.g., in vivo or ex vivo). Polynucleotides (e.g., genes) encoding the tumor associated antigens may be edited at selected target sites by nucleobase editors comprising a catalytically-inactive Cas9 and a cytosine deaminase, leading to the expression of heteroclitic or cryptic peptides that are more immunogenic than the native peptide derived from the tumor associated antigens. The heteroclitic or cryptic peptide elicit strong tumor-specific immune response (e.g., T-cell response or B-cell response), which inhibits tumor growth and metastasis.

The present disclosure provides oligonucleotides, methods, and compositions for degrading RNA via the lysosomal pathway. Also contemplated are oligonucleotides, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with EXOC2, Ku80, and Task1 in a subject in need thereof.

It is disclosed a method for determining the biological activity of defibrotide, which comprises the steps of: a) bringing into contact defibrotide, mammalian euglobulin and a substrate specific for the plasmin which, by reaction with the plasmin, provides a measurable product; and b) measuring the amount of product formed at successive times, to thereby determine the biological activity of the defibrotide. Liquid defibrotide formulations are also disclosed, preferably water solutions, having a defined biological activity and, in particular, having an activity of 25 to 35 IU / mg of defibrotide, preferably from 27 to 32 IU / mg and, more preferably, from 28 to 32 IU / mg.

The invention relates to the technical field of gene engineering, in particular to nucleic acid for encoding kreotoxin and a preparation method of the kreotoxin. The invention provides nucleic acid for encoding the botulinum toxin, the nucleic acid is subjected to codon optimization, and the scheme is proved to be superior to other optimized sequences. Through verification, the sequence has a relatively high expression quantity in escherichia coli and is in soluble expression, and the prepared kreotoxin has good activity.

The invention relates to a siRNA for targeted regulation of PCSK9 gene expression and a use thereof. Experimental results show that some oligonucleotide sequences subject to alternate modification and specific template modification can significantly inhibit PCSK9 expression, and can be used for developing a drug for treating PCSK9-related diseases.

A phosphate-free automatic dishwashing cleaning composition comprising: a) from 10% to 50% by weight of the composition of an organic complexing agent system comprising at least 10% by weight of the composition of methyl glycine diacetic acid; b) an amylase; and c) a protease wherein the protease is a variant having at least 90% identity with the amino acid sequence of SEQ ID NO: 1 and comprising at least one amino acid substitution (using the SEQ ID NO:1 numbering) selected from the group consisting of S39E, S99R, S126A-D127E-F128G, N242D and mixtures thereof; or d)a protease wherein the protease is a variant having at least 90% identity with the amino acid sequence of SEQ ID NO:2 and comprising at least one amino acid substitution (using the SEQ ID NO:2 numbering) selected from the group consisting of X39E, X126A-X127E-X128G, X242D and mixtures thereof.

The invention discloses an interfering RNA (Ribonucleic Acid) for inhibiting a PCSK9 gene and application of the interfering RNA. The interfering RNA comprises any one or more than two nucleotide sequences as shown in SEQ ID NO: 1-40 and SEQ ID NO: 73-96. The interfering RNA can better target and silence mRNA of the liver PCSK9, reduce the protein level of the PCSK9, enhance LDL-C metabolism and reduce serum cholesterol, and a solid technical basis is provided for research and development of siRNA drugs for prevention and treatment of PCSK9 gene mediated diseases and symptom relief.

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 present disclosure provides proteins useful for preventing, treating, suppressing and / or eliminating infestations and infections of plants by various phytopathogenic pests, as well as formulations comprising such proteins, polynucleotides encoding such proteins, organisms expressing such proteins, and methods of using such proteins, formulations, polynucleotides and organisms in agriculture and other fields of endeavor.

The invention discloses a method for preparing a simeglutide precursor peptide through intracellular enzyme digestion. The method comprises the following steps: (1) connecting a dissolution-promoting tag GST and the simeglutide precursor peptide together through protease specific recognition of amino acid sites to form a fusion protein; (2) integrating the coding nucleotide sequence of the fusion protein, the coding nucleotide sequence of KEN2 protease and the coding nucleotide sequence of carboxypeptidase B into the same expression vector to form a recombinant vector; (3) transforming the recombinant vector into engineering bacteria and carrying out fermentation production; and (4) centrifuging a fermentation product, collecting thalli, and purifying to obtain the precursor peptide powder of the semeglutide. The whole operation process is simpler, more convenient and smoother, tedious recovery steps are omitted, and the preparation and recovery difficulty of the precursor peptide of the semeglutide is remarkably reduced.

In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to lipid nanoparticles for use as drug delivery agents. The lipid nanoparticles are composed of lipopeptide conjugates, where a peptide is bonded to a lipid. The lipid nanoparticles described herein represent a new approach in drug delivery, addressing critical challenges in balancing biodegradability, biocompatibility, and organspecific targeting. The lipid nanoparticles can selectively target and deliver bioactive agents to specific tissues in a subject by modifying specific amino acids and ratios thereof in the peptide of the lipopeptide conjugate.