73 results about "Adenosine deaminase" patented technology

The invention relates to the field of preparation and application of biological peptides, in particular to a swelling hippocampal peptide and application thereof in preparation of uric acid reducing and gout resisting products. The amino acid sequence is shown as SEQ ID NO.1. The uric acid reducing effect of the compound is proved through in-vitro xanthine oxidase (XOD) and adenosine deaminase (ADA) inhibition experiments and cell experiments; on the basis, the uric acid reducing and gout resisting activity of the peptide sequence is further verified by means of a hyperuricemia animal model. The achievement provides a solid theoretical support for high-value development and utilization of the hippocampus japonicus and research and development of uric acid reducing and gout resisting related products.

The present disclosure provides adenosine deaminase, fusion proteins, base editor systems and uses, and specifically provides an adenosine deaminase polypeptide having an amino acid sequence having at least about 70%, 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% sequence identity to SEQ ID NO: 13. Also provided are novel nucleic acid modified enzymes having improved efficiency, compositions of base editors comprising the same, and methods and uses for editing target sequences using these adenosine deaminase variants.

The application discloses application of total flavones of chrysanthemum morifolium ramat and metabolites thereof in preparation of uric acid-lowering or liver and kidney protecting drugs or health care products. The total flavones of chrysanthemum morifolium ramat contain various flavone compounds. In a hyperuricemia model mouse, the total flavones of chrysanthemum morifolium ramat can significantly reduce blood uric acid level, and has a significant protective effect on liver and kidney, and the effect is achieved by inhibiting the activity and expression of xanthine oxidase and adenosine deaminase in the liver, and regulating the expression of uric acid related transporters in the kidney. Meanwhile, metabolites of the total flavones of chrysanthemum morifolium ramat, luteolin-7-O-glucuronide and apigenin-7-O-glucuronide, can also play a pharmacological role in the mouse body. In vitro experiments and mouse primary hepatocytes further prove that luteolin-7-O-glucuronide and apigenin-7-O-glucuronide have an inhibiting effect on the activity and expression level of xanthine oxidase. The application widens the application range of traditional Chinese medicinal materials, and provides a new direction for development of efficient and low-toxic uric acid-lowering and anti-gout drugs or health care products.

The invention provides a composition for reducing uric acid and relieving gout and a preparation method thereof, and relates to the technical field of products for reducing uric acid and relieving gout. The composition comprises the following raw materials: 18-24 parts of phellinus igniarius, 9-13 parts of sunflower disc small molecule peptide extract, 3-7 parts of corn stigma, 4-6 parts of poria cocos, 2-5 parts of pawpaw, 3-6 parts of liquorice, 2-5 parts of astragalus extract and 3-6 parts of lettuce extract. The preparation method of the sunflower disc small-molecule peptide extract comprises the following steps: carrying out enzymolysis on sunflower disc powder twice, carrying out membrane filtration to obtain a sunflower disc small-molecule peptide solution, reacting the sunflower disc small-molecule peptide solution with chitosan oligosaccharide and transglutaminase, and carrying out freeze drying to obtain the sunflower disc small-molecule peptide extract. Through the proper raw material composition and proportion, the metabolic function can be effectively regulated to promote excretion of uric acid, so that the content of xanthine oxidase and adenosine deaminase in the liver is obviously reduced, the uric acid level is effectively reduced, the intestinal probiotic structure can be stabilized, the immunity is enhanced, the kidney is protected, and the good effects of reducing uric acid and relieving gout are achieved.

The utility model provides a transport frame for adenosine deaminase assay kits, which comprises a trolley body, vertical plates are symmetrically arranged at the upper part of the trolley body, a plurality of groups of placing components are uniformly arranged between the two vertical plates along the vertical direction, and each group of placing components comprises a mounting plate which is connected to the opposite surfaces of the two vertical plates through a mounting part; the installation parts are used for adjusting the inclination angles of the installation plates and all parts on the installation plates, and a containing plate is arranged on the lower portions of the two installation plates. The two vertical plates are matched with the plurality of groups of placing assemblies, so that the biochemical components of the adenosine deaminase determination kit and the biochemical components in the determined reagent tube can be separately placed and stored, and the influence on the detection sensitivity and accuracy is avoided.

The present application relates to the preparation and application field of biological peptide, and more particularly to a hippocampus abdominalis peptide and its application in preparation of products for reducing uric acid and resisting gout. The amino acid sequence is shown as SEQ ID NO. 1, and the present application confirms the uric acid reducing effect through in vitro xanthine oxidase (XOD) and adenosine deaminase (ADA) inhibition experiments and cell experiments; on this basis, the uric acid reducing and gout resisting activity of the peptide sequence is further verified by means of a high uric acid animal model. This achievement provides a solid theoretical support for high-value development and utilization of hippocampus abdominalis, and research and development of products for reducing uric acid and resisting gout.

The present application provides an engineered circular RNA capable of recruiting adenosine deaminase acting on RNA (ADAR; arRNA) and its application in treating Duchenne muscular dystrophy (DMD).

The application provides an adenosine deaminase content detection method and application thereof. The adenosine deaminase content detection method comprises the following steps: using the intrinsic fluorescence of adenosine, using adenosine deaminase to hydrolyze adenosine, and detecting the content of adenosine deaminase by a fluorescence analysis method. Adenosine itself has strong fluorescence, and after being hydrolyzed by adenosine deaminase, the fluorescence of the obtained hydrolysis product is reduced, thereby causing the fluorescence intensity of the solution of the detection system to be reduced; the content of adenosine deaminase in the system is detected by the change of the fluorescence intensity before and after adenosine hydrolysis. The adenosine deaminase content detection method in the application is simple to operate, does not need large instruments and equipment, and is cheap and easy to obtain materials, can accurately and rapidly detect the content of adenosine deaminase in a sample to be detected, has good sensitivity and specificity, and has a relatively wide application prospect.

The invention discloses a walnut-derived xanthine oxidase inhibitory peptide and application thereof, and belongs to the technical field of bioactive peptide biology. The amino acid sequence of the xanthine oxidase inhibitory peptide provided by the invention is as shown in SEQ ID No. 1. Through in-vitro activity determination, the IC50 value of the inhibitory peptide is 3.34 mg / mL, and it is proved that the inhibitory peptide has high inhibitory activity on xanthine oxidase. Besides, the inhibitory peptide can reduce the levels of creatinine, urea nitrogen, adenosine deaminase, glutamic oxalacetic transaminase and glutamic-pyruvic transaminase, regulate the expression of kidney uric acid resorption protein URAT1, uric acid excretion protein GLUT9 and ABCG2, and significantly reduce the generation of uric acid, can be used for inhibiting xanthine oxidase and preventing or improving hyperuricemia, is applied to preparation of drugs for improving hyperuricemia, and has broad application prospects. The medicine takes the active peptide as the only active ingredient or one of the active ingredients, and has a good application prospect.

The present invention discloses an adenosine deaminase mutant, which is a C141R and L144P mutant based on the wild type. The present invention also discloses a Pichia pastoris base editor containing the adenosine deaminase mutant. The Pichia pastoris base editor can achieve precise editing of specific base sites in the Pichia pastoris genome, providing a gene editing tool for basic and applied research based on Pichia pastoris.

A fusion protein comprising: a first component comprising an antibody, or a fragment or variant thereof; and a second component comprising a cytokine trap or an adenosine deaminase or a fragment or variant thereof. In certain embodiments, the antibody is an anti-PD-1 antibody. In certain embodiments, the antibody binds to a tumor antigen, for example a MUC16 or MUC1 antigen. In certain embodiments, the cytokine trap is a TGF-β trap. A polynucleotide encoding such a fusion protein and a vector comprising such a polynucleotide. A composition comprising the fusion protein. A method of using the composition, including in the treatment of cancer.

This application belongs to the field of biotechnology and relates to an efficient and specific editing system, method, and application for A-G base substitution. The fusion protein described in this application comprises, from the N-terminus to the C-terminus, a first SaCas9 nickase fragment, a chimeric deaminase fragment, and a second SaCas9 nickase fragment. The deaminase is selected from adenosine deaminase or a variant thereof, specifically ecTadA8e. The amino acid sequence of ecTadA8e is shown in SEQ ID NO. 20, or has more than 80% sequence identity with the amino acid sequence shown in SEQ ID NO. 20, and possesses the function or activity of ecTadA8e. The fusion protein provided in this application, combined with the corresponding guide RNA, can efficiently and specifically replace the base A with G at the target site, providing an effective tool for repairing pathogenic mutations, studying gene function, and improving cell function, and has promising application prospects.

The present invention relates to methods and compositions for disrupting interaction of an NRF2 protein and a KEAP1 protein. The methods include contacting at least one polynucleotide selected from the group consisting of a polynucleotide encoding the NRF2 protein and a polynucleotide encoding the KEAP1 protein with a guide oligonucleotide that effects one or more (e.g., at least two) adenosine deaminase acting on RNA (ADAR)-mediated adenosine to inosine alterations in said at least one polynucleotide, wherein the adenosine to inosine alterations generate a mutant amino acid, thereby disrupting interaction of the NRF2 protein and the KEAP1 protein. The invention also relates to methods of treating a KEAP1-NRF2 pathway related disease in a subject in need thereof, the method comprising contacting, within the subject, at least one polynucleotide selected from the group consisting of a polynucleotide encoding an NRF2 protein and a polynucleotide encoding a KEAP1 protein with a guide oligonucleotide that effects an adenosine deaminase acting on RNA (ADAR)-mediated adenosine to inosine alteration in said at least one polynucleotide, wherein the adenosine to inosine alteration generates a mutant amino acid, thereby disrupting interaction of the NRF2 protein and the KEAP1 protein and treating the disease in the subject; and compositions thereof.

The invention relates to chemically modified oligonucleotides for use in site-directed A-to-I editing of a target RNA inside a cell with endogenous adenosine deaminase acting on RNA (ADAR), the oligonucleotide comprising a sequence capable of binding to a target sequence in a target RNA and a central base triplet (CBT) of 3 nucleotides (N−1N0N+1), wherein N0 is the central nucleotide directly opposite to a target adenosine in the target RNA that is to be edited, wherein the oligonucleotide comprises at least one internucleoside linkage that is a methanesulfonyl (mesyl) linkage.

The invention relates to the technical field of lactobacillus rhamnosus, in particular to lactobacillus rhamnosus and application thereof in intervention of uric acid synthesis. The strain is lactobacillus rhamnosus LRa06 of which the preservation number is CGMCC (China General Microbiological Culture Collection Center) NO.33730. The strain has an inhibition effect on metabolic enzymes in a uric acid synthesis route, and especially has an inhibition effect on adenosine deaminase and xanthine oxidase. The strain inhibits uric acid synthesis and reduces serum urate by inhibiting metabolic enzymes of the two uric acid synthesis pathways, and has application prospects in preparation of uric acid reducing preparations.

A chemically modified polynucleotide encoding a fusion protein, wherein the chemically modified polynucleotide comprises a sequence of SEQ ID NO: 701 is claimed wherein the fusion comprises a Cas9 nickase and and deaminase, such as an adenosine deamnase TadA. and which further comprises a protospacer found on a gene encoding Angiopoietin-like 3 protein (ANGPTL3). The chemical modifications may include phosphorothioate linkages and 2'-O-methyl modfied nucleosides. Use of such fusions in treating cardiovascular conditions is further claimed. [Figure 3]

The invention relates to the technical field of hyperuricemia, in particular to lactobacillus reuteri and application thereof in reducing uric acid. The bacterial strain is lactobacillus reuteri WP503 of which the preservation number is CGMCC (China General Microbiological Culture Collection Center) NO.34900, and the bacterial strain is a lactobacillus reuteri WP503 of which the preservation number is CGMCC NO.34900. The bacterial strain has an inhibition effect on metabolic enzymes in a uric acid synthesis route, and especially has an inhibition effect on adenosine deaminase (ADA, EC 3.5. 4.4) and xanthine oxidase (XOD, EC 1.17. 3.2). The strain inhibits uric acid synthesis and reduces the content of serum urate by inhibiting metabolic enzymes of the two uric acid synthesis pathways, and has application prospects in preparation of uric acid reducing preparations.

The application discloses a fusion protein, an in-vivo directed evolution system and application thereof, and the fusion protein comprises a Retron reverse transcriptase and an adenosine deaminase, and the adenosine deaminase is connected to the N terminal or C terminal of the Retron reverse transcriptase. The application firstly fuses the Retron reverse transcriptase with the adenosine deaminase TadA-8e, constructs a bifunctional fusion protein system with reverse transcription activity and adenosine deamination activity, realizes the functional coupling of Retron-mediated msDNA synthesis and adenosine deamination mutation introduction. The application significantly improves the mutation frequency and mutation diversity of a target gene, accelerates the generation, accumulation and fixation of beneficial mutations, and thus improves the in-vivo directed evolution efficiency.

The invention provides compositions and methods for delivering first and second polynucleotides each encoding a fragment of an A-to-G Base Editor fusion protein comprising one or more deaminases (e.g., adenosine deaminases) and nCas9, wherein the first polynucleotide encodes an N-terminal fragment of nCas9 fused to an intein-N of a split intein pair and the second polynucleotide encodes a C-terminal fragment of nCas9 fused to an intein-C of a split intein pair, and methods for delivering these fragments together with an sgRNA to a cell (e.g., AAV delivery), where the fragments are spliced together by a split intein system, thereby reconstituting a functional base editing system in the cell.

This invention provides a pharmaceutical composition for the treatment of hereditary contralateral pigmentary disorders, a mouse model for hereditary contralateral pigmentary disorders, and a screening method for compounds for the treatment of hereditary contralateral pigmentary disorders. [Solution] A heterozygous Adar1 knockout mouse that has lost the function of Adar1 (Adenosine Deaminase Acting on RNA1) throughout the body and exhibits a phenotype of mottled skin and / or fur color.

The application discloses camel milk hypouricemic peptides with a hypouricemic effect and application thereof, and the amino acid sequence of the camel milk hypouricemic peptides is QPWMQ. The camel milk hypouricemic peptides can significantly inhibit the activity of xanthine oxidase (XOD) and / or adenosine deaminase (ADA), reduce the uric acid concentration in the body, maintain the normal level of uric acid in blood, and prevent and treat hyperuricemia; and the application fully excavates small-molecule bioactive substances of camel milk, and improves the nutritional value and economic value of camel milk.

The present invention relates to a single base editor using adenosine deaminase acting on RNA (ADAR enzyme) and a single base editing method using same. Specifically, the present invention relates to a single base editor using an ADAR enzyme and a single base editing method using same, wherein the single base editor solves the problem of not only a target single base but also all single bases around the target single base being replaced, which is the biggest limitation of conventional base editing tools, and can selectively replace just a single base.

The invention discloses a camel milk uric acid reducing peptide with a uric acid reducing effect and application thereof. The amino acid sequence of the camel milk uric acid reducing peptide is QPWQ. The camel milk uric acid lowering peptide can significantly inhibit the activity of xanthine oxidase (XOD) and / or adenosine deaminase (ADA), reduce the uric acid concentration in a body, maintain the normal level of uric acid in blood, and prevent and treat hyperuricemia; according to the invention, the micromolecular bioactive substances of the camel milk are fully excavated, and the nutritional value and economic value of the camel milk are improved.

Provided is a method for controlling the translation amount of a target protein based on target RNA that encodes the target protein. The method for controlling the translation amount of a target protein includes editing a base sequence represented by AUA or AUG included in a 5' untranslated region of mRNA including a coding region of a target protein into a base sequence represented by AUI or IUG in the presence of adenosine deaminase. The method may include: editing at least one of the base sequences represented by AUG included in the 5' untranslated region of the mRNA serving as a target into a base sequence represented by IUG; and setting the number of base sequences represented by AUG included in the 5' untranslated region after editing to 1 or less. The method may also include editing at least one of the base sequences represented by AUA included in the 5' untranslated region of the mRNA serving as a target into a base sequence represented by AUI, and the number of base sequences represented by AUG included in the 5' untranslated region may be 0.

Systems and methods for predicting deamination efficiency or specificity associated with a guide RNA (gRNA) are provided. A nucleic acid sequence for the gRNA is received. Responsive to inputting a data structure into a model, a metric for an efficiency or specificity of deamination by a first Adenosine Deaminase Acting on RNA (ADAR) protein of a target nucleotide position in mRNA transcribed from a target gene is obtained as output from the model. The data structure includes an encoding of the nucleic acid sequence for the gRNA.

The invention features compositions and methods for modifying a polynucleotide (e.g., DNA) using a nucleobase editor comprising a first DNA binding protein domain that is catalytically inactive, a domain having base editing activity, and a second DNA binding protein domain having nickase activity. The invention also features a fusion protein comprising a domain having base editing activity (e.g., cytidine deaminase or adenosine deaminase), and two nucleic acid programmable DNA binding protein domains (napDNAbp), a first napDNAbp comprising nickase activity and a second napDNAbp that is catalytically inactive, where at least the two napDNAbps are joined by a linker, as well as related methods for using such base editors, and kits comprising the base editors.

Disclosed herein is a readrRNA (RNA sensing by Endogenous ADAR) molecule comprising a modular RNA molecule that facilitates sensing and detection of a cell type or its status, including a cell of a mammalian nervous system, including neurons and / or neuronal cells of the area postrema of the mammalian brain, and / or facilitates delivery of an effector protein to the selected cell. A composition that includes such a modular RNA molecule and another nucleic acid (linked or unlinked to the modular RNA molecule) is a CellREADR (Cell access through RNA sensing by Endogenous ADAR). CellREADR senses the presence of a selected cell RNA in a cell of a mammalian nervous system via readrRNA and leverages RNA editing mediated by ADAR (adenosine deaminase acting on RNA) for coupling the detection of a cell-defining RNA with translation of one or more effector proteins in a cell of a mammalian nervous system.

The present invention features genetically modified immune cells comprising novel adenosine base editors (e.g., ABE8) having enhanced anti-neoplasia activity, resistance to immune suppression, and decreased risk of eliciting a graft-versus-host reaction or host-versus-graft reaction, or a combination thereof. The present invention also features methods for producing and using these modified immune effector cells.

The present invention features genetically modified immune cells comprising novel adenosine base editors (e.g., ABE8) having enhanced anti-neoplasia activity, resistance to immune suppression, and decreased risk of eliciting a graft-versus-host reaction or host-versus-graft reaction, or a combination thereof. The present invention also features methods for producing and using these modified immune effector cells.