48 results about "Uridine" patented technology

The present disclosure provides compositions and methods for inserting heterologous payload sequences into a target-site in a host cell genome. The compositions and methods use non-LTR retrotransposon reverse transcriptase proteins that bind template RNAs comprising a payload sequence that encodes a protein or regulatory RNA. The template RNA can comprise modified uridines that are not cleavable by a ribozyme. The incorporation of modified uridines increases the efficiency of integration and expression of the payload sequence and decreases cellular toxicity.

The invention discloses a multi-emission composite nano ratiometric fluorescent probe for detecting fluoroquinolone antibiotics and a preparation method of the multi-emission composite nano ratiometric fluorescent probe. The CdTe-Tb-UMP composite nano ratiometric fluorescent probe with double ligands is prepared by taking metal terbium ions (Tb < 3 + >) as central ions and respectively taking uridine monophosphate (UMP) and CdTe quantum dots with red fluorescence emission as bridged ligands. ENR is further coordinated with Tb < 3 + >, energy is transferred to Tb < 3 + > through an antenna effect, so that characteristic green fluorescence of Tb < 3 + > is turned on, and fluorescence of CdTe quantum dots is almost kept unchanged. On the basis, a portable nursing point testing system is further constructed, and the portable nursing point testing system comprises an intelligent mobile phone detector and a wearable fingertip sensor integrated with a micro-fluidic chip and is used for on-site rapid detection of the ENR. The paper-based chip shows rapid and sensitive fluorescence response, and the detection limits of the spectrograph and the paper-based sensor on the ENR are 4.7 nM and 13.1 nM respectively. The probe can be applied to detection of ENR in actual environment water samples, food and drugs.

Disclosed are in vitro transcribed (IVT) messenger RNAs (mRNAs) comprising a polynucleotide that encodes human TJP2 gene, a 5' terminal cap, and a poly-adenylation (poly- A) tail at the 3' terminal end. In aspects, the polynucleotide is substantially free of uridine bases and comprises pseudouridine bases. Methods, compositions and uses employing the IVT mRNA for treating or preventing progressive familial intrahepatic Cholestasis type IV (PFIC type 4) in a patient in need thereof is also disclosed.

The present invention relates to a photosensitive RNA cytidine base editor and use thereof. The photosensitive RNA cytidine base editor can cause deamination of cytidine (C) in a target double-stranded RNA to uridine (U), thereby achieving editing of C to U. The photosensitive RNA cytidine base editor comprises: (1) a dCas-eADAR2dd N-pMagHigh fusion protein, and (2) an nMagHigh-eADAR2dd C fusion protein.

The invention relates to a uridine diphosphate-glucose dehydrogenase mutant and an application of the uridine diphosphate-glucose dehydrogenase mutant in synthesis of uridine diphosphate-glucuronic acid. The amino acid sequence of the uridine diphosphate-glucose dehydrogenase mutant D7P166M / I169A is as shown in SEQ ID NO. 2, and the nucleotide sequence of the coding gene is as shown in SEQ ID NO. 1. The invention also provides an application of the mutant in preparation of uridine diphosphate-glucuronic acid, and a method for preparing uridine diphosphate-glucuronic acid by using the mutant. Experimental determination shows that the melting temperature of the mutant is increased by 30 DEG C compared with that of a wild type, the activity is improved by 20%, and a powerful tool is provided for enzymatic synthesis of uridine diphosphate-glucuronic acid compounds. Compared with a conventional synthesis pathway, the method for synthesizing uridine diphosphate-glucuronic acid through immobilized enzyme flow provided by the invention can be used for stably and efficiently synthesizing for a long time, and is beneficial to reducing the cost and realizing industrial synthesis.

The invention relates to the technical field of biology, and discloses a recombinant N-acetylglucosamine-1-phosphate uridine transferase (GlmU) mutant and a preparation method thereof. The sequence of the recombinase is formed by connecting an N-acetylglucosamine-1-uridine phosphate transferase (GlmU) mutant (L113V-V172I) from Azotobacter chroococcum, an N-terminal histidine tag (His-tag) and a small ubiquitin-like modified protein tag (SUMO-tag) in series. The invention further discloses a preparation method of the recombinase. Compared with a recombinant wild type N-acetylglucosamine-1-uridine phosphate transferase with the same source, the recombinant N-acetylglucosamine-1-uridine phosphate transferase mutant has higher activity which is 1.5 times of that of the recombinant wild type and higher stability, and the residual activity of the mutant is 66.5% after the mutant is placed at room temperature for 5 days, so that the mutant has a good application prospect in the field of N-acetylglucosamine-1-uridine phosphate transferase. And the soluble expression quantity of the recombinant mutant N-acetylglucosamine-1-uridine phosphate transferase is increased by 5 times.

The present disclosure provides compositions and methods for inserting a heterologous payload sequence into a target site in the genome of a host cell. The compositions and methods use a non-LTR reverse transcriptase reverse transcriptase protein that binds to a template RNA comprising a payload sequence that encodes the protein or regulates the RNA. The template RNA may comprise a modified uridine that cannot be cleaved by a ribozyme. The incorporation of the modified uridine increases the integration and expression efficiency of the payload sequence and reduces cytotoxicity.

Click-labeled uridine bases, nucleosides, and phosphoramidites are provided, including improved methods of synthesis, oligonucleotides comprising the click-labeled nucleosides, methods of synthesizing spin-labeled oligonucleotides using click-labeled nucleotides, and spin-labeled oligonucleotides comprising click-labeled nucleosides.

The application provides a radix isatidis granule and a preparation method thereof, which is prepared from the following components in parts by weight: radix isatidis 700 parts, sucrose 170-190 parts and dextrin 50-70 parts. The content of active ingredient (R,S)-deoxyschizandrin, the total content of uridine, guanosine and adenosine, and the content of indirubin in the prepared radix isatidis granule are significantly improved, and the quality is stable after being accelerated for 6 months.

The present disclosure relates to the identification of a novel nucleoside modification, referred to herein as anhydride U, present in tRNA molecules within the cell. The present disclosure further relates to the enzymatic and chemical production of anhydride U as well as methods for detecting and regulating the presence of anhydride U within the cell.

The present invention discloses a quality control method for Homalomena occulta samples, which comprises the following steps: respectively sucking a reference medicinal material reference solution, a reference substance reference solution of reference substance and a test solution for ultra-high performance liquid chromatography analysis, constructing a characteristic chromatogram of the Homalomena occulta samples to be tested, wherein the characteristic chromatogram includes characteristic peak 2 with the same retention time as the reference peak of uridine reference substance and characteristic peak 3 with the same retention time as the reference peak of osbeckianic acid reference substance; carrying out qualitative analysis on the Homalomena occulta samples to be tested through the obtained characteristic chromatogram; and / or taking osbeckianic acid as an index for content determination to carry out quantitative analysis on the Homalomena occulta samples to be tested. The content index established by the present invention has stronger specificity, has a high content in the Homalomena occulta samples to be tested, and can accurately reflect the quality characteristics of the Homalomena occulta samples; the established methods for content determination and characteristic chromatogram can simultaneously distinguish true and false Homalomena occulta, and the results are relatively objective and accurate.

Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and / or one or more abasic spacers and / or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

The invention relates to a uridine diphosphate-glucuronyl transferase mutant and an application of the uridine diphosphate-glucuronyl transferase mutant in catalytic synthesis of glucuronide. The amino acid sequence of the uridine diphosphate-glucuronyl transferase mutant is as shown in SEQ ID NO. 2, and the nucleotide sequence of the coding gene is as shown in SEQ ID NO. 1. The invention provides a uridine diphosphate-glucuronyl transferase mutant with high activity and high stability. Compared with wild uridine diphosphate-glucuronyl transferase, the uridine diphosphate-glucuronyl transferase mutant has mutation of 10 amino acid sites. According to experimental determination, the melting temperature of the mutant is increased by 24 DEG C compared with that of a wild type, the activity is increased to 1.65 times, the expression quantity is increased to 4.2 times, and a powerful tool is provided for enzymatic synthesis of glucuronide compounds.

The invention provides an isatis root quality evaluation method based on a digital characteristic fingerprint spectrum and multi-index determination and application, and belongs to the technical field of natural pharmaceutical chemistry. According to the method, a digitized characteristic fingerprint spectrum of radix isatidis is obtained based on parameters such as common peaks and N strong peaks, and on the basis of the digitized characteristic fingerprint spectrum, the characteristic fingerprint difference rate is taken as the center, and on the basis of content determination of index components such as uridine, guanosine, (R, S)-epigoitrin and adenosine, the characteristic fingerprint N strong peaks, the characteristic fingerprint N strong peaks and the characteristic fingerprint N strong peaks are matched with the characteristic fingerprint N strong peaks. According to the method, parameters such as the characteristic fingerprint overlapping rate and the detection rate are systematically clustered, common key characteristics of all samples can be represented, differences among different samples can be well reflected, reasons for differences of different isatis root samples can be reflected from different dimensions through multi-index component content determination and confluence analysis, and the method has the advantages of high accuracy and high accuracy. The difference of the radix isatidis samples is divided into the difference with high index component content or proportion composition, the difference with low index component content or proportion composition and the like.

An enzyme has an activity that converts uridine in RNA to cytidine. A complex includes: the enzyme; and a sequence recognition module that allows the enzyme to act specifically on uridine that has occurred in mRNA due to mutation.

This invention relates to the field of fermentation engineering technology, and particularly to a mutant of uridine 5′-bisphosphate-N-acetylglucosamine 2 epimerase and its application. The mutant is based on the amino acid sequence of uridine 5′-bisphosphate-N-acetylglucosamine 2 epimerase, including any one of the following: i) a mutation of S263Q or S263L; ii) in addition to i), a mutation of one of F266W, F266Y, F266I, or F266L. This invention has discovered multiple mutation modes of uridine 5′-bisphosphate-N-acetylglucosamine 2 epimerase, and its application in the construction of sialyl lactose-producing *Escherichia coli* can effectively increase the yield of sialyl lactose, which has significant application value in the field of sialyl lactose production.

The present application provides methods, compositions, and systems for targeted pseudouridylation of RNA. In some aspects, the present application provides methods for editing a target RNA (e.g., mRNA) in a host cell, comprising introducing an engineered guide small nucleolar RNA (gsnoRNA) into the host cell, wherein the gsnoRNA recruits a DKC1 protein to modify a target uridine residue in the target RNA to a pseudouridine residue. In some embodiments, the DKC1 protein has cytoplasmic localization in the host cell.

The present disclosure provides pyrimidine nucleoside compounds, including torcitabine, thymidine, deoxyuridine, deoxycytidine and uridine, and methods to treat telomere biology disorders (TBDs) and aging-related diseases, including hematological disorder, liver disease, or hepatic fibrosis, comprising administering to a subject diagnosed with said telomere biology disorder a therapeutically effective amount of said compounds.

The present application relates to a kind of preparation method of triphosphoryl uridine trisodium and its preparation.The present application uses ionic liquid as reaction solvent, 2-chloro-4H-1,3,2-benzene dioxaphosphorin-4-ketone (compound 1) is reacted with tributylammonium pyrophosphate to generate cyclic intermediate 2, then uridine is reacted, and then it is obtained by oxidation, basic hydrolysis ring-opening step triphosphoryl uridine trisodium.The present application uses ionic liquid as solvent to promote the site selectivity of the hydroxyl group in the ribose structure of uridine in the reaction, which can make the reaction intermediate 2 react with the hydroxyl group of the 5' position of uridine with high selectivity, so as to obtain UTP with high yield, and the present application also prepares UTP into the form of trisodium salt to facilitate purification and preservation.The present application solves the problems of long steps and low yield in the prior art when using chemical synthesis method to synthesize UTP.

The present application relates to a kind of RNA base editing method and editing tool for recruiting endogenous APOBEC family enzyme by APOBEC recruiting guide RNA (APOBEC-recruiting guide RNA, rgRNA) to convert target cytosine into uridine. The rgRNA includes: at least one APOBEC recruiting domain and at least one programmable antisense region, when the rgRNA is combined with the target RNA, an editing loop that induces a circular single-stranded structure on the target RNA sequence. In the way of "catch recruit execute", accurate and flexible base conversion is realized, and the boundary of RNA editing in gene regulation and therapeutic application is expanded.

The invention discloses a mechanism for promoting colorectal cancer through macrophage polarization and an IL-17 (interleukin-17) pathway by Streptococcus gallyticus streptococcus metabolite and application of the Streptococcus gallyticus streptococcus metabolite, and relates to the technical field of microorganism-tumor immunoregulation. According to the invention, specific metabolites, namely inosine-5 '-monophosphate (IMP), methionine, uridine and creatine, in a Streptococcus gallyticus supernatant promote CRC (cyclic redundancy check) through the following two paths: M2 polarization of macrophages: TAM infiltration of tumor-related macrophages is remarkably increased, an immunosuppressive microenvironment is induced, and tumor growth is promoted; and IL-17 signal channel activation: RNA-seq shows that the IL-17 channel is the most significant enrichment channel, the expression of IL-17F and IL-22 is specifically up-regulated, and inflammation and tumor progression are promoted. The invention reveals that the Sg metabolite is a key driving factor of CRC instead of bacteria for the first time, reveals a mechanism that the Sg metabolite activates and promotes colorectal cancer through macrophage M2 polarization and IL-17 pathway, provides an application value of the Sg metabolite in CRC diagnostic marker screening and targeted therapeutic drug development, and provides a new idea for CRC diagnosis and treatment.

Compositions and methods comprising an artificial poly (A) sequence having at least one cytosine and at least one uridine and / or guanosine are provided.

The application provides a cytosine nucleoside producing strain and a construction method and application thereof, and the strain is constructed by using CRIPSR / Cas9 gene editing technology E. coli The cdd gene and cmk gene are knocked out on the UR12 genome, the nucleoside triphosphate reductase gene nrdD is weakened, and the nucleoside triphosphate pyrophosphatase gene nudG, the nucleoside diphosphate kinase gene ndk and the uridine acid kinase gene pyrH carrying a mutation point are overexpressed (D93A) The cytosine triphosphate synthase gene pyrG carrying a mutation point is introduced into the Corynebacterium glutamicum heterologously and in multiple copies (D160E、E162A、E168K，cgl) The bifunctional nucleotidase gene of Saccharomyces cerevisiae PHM8 (sce) The obtained strain has good genetic stability, high fermentation yield and can stably produce cytosine nucleoside.

The present application provides compositions and methods for preparing and using “heavy” nucleotide derivatives of thymidine or uridine by replacing the oxygen atom attached to one or more of positions with non-radioactive oxygen-18 (18O), administering it to a subject to target a tumor including incorporation into tumor cell DNA, and then treating the tumor with proton beam therapy to transmutate the 18O to 18F, resulting in a break of the new fluorine-phosphorous bond. This chemical event destabilizes ribose-phosphate DNA back-bone and base pairing thus produce single- and double strand breaks, clusters lesions that can lead to irreparable DNA damage and enhanced tumor cell killing. The atomic, chemical, and physical aspects result in the use of lower radiation doses and significantly alter acute and late morbidity of radiotherapy. Heavy thymidine and heavy uridine derivatives labeled with 18O have been made and tested.

The invention relates to C2 '-alkyl substituted nucleoside which comprises at least one of C2'-alkyl substituted thymidine, C2 '-alkyl substituted uridine, C2'-alkyl substituted adenosine and C2 '-alkyl substituted guanosine. The structure of the C2 '-alkyl substituted nucleoside is shown as a formula I or a formula II; the structure of the C2 '-alkyl substituted uridine is shown as a formula III in the specification; the structure of the C2 '-alkyl substituted adenosine is shown as a formula IV; the structure of the C2 '-alkyl substituted guanosine is shown as a formula V. The invention also relates to a preparation method of the C2 '-alkyl substituted nucleoside. According to the C2 '-alkyl substituted nucleoside and the preparation method thereof, the limitation of the prior art on functional group compatibility and operation convenience can be broken through, and the synthesis path of the C2'-alkyl substituted nucleoside can be enriched, so that the research and development process of oligonucleotide drugs is greatly promoted.

The present invention provides a method for detecting nucleosides and its application. The method described in the present invention uses ultra-high performance liquid chromatography (UPLC) to detect the active ingredients in CHO host cell culture medium and cell culture supernatant. The method can quickly detect the components and contents of 6 nucleosides, namely cytidine, hypoxanthine, uridine, guanosine, thymidine and adenosine, simultaneously within 15 minutes.

The invention provides a method for supporting operable activities in daily life by providing a combination of (a) long chain polyunsaturated fatty acids - in particular DHA and / or EPA - with (b) a nucleoside or nucleotide - in particular uridine or an equivalent thereof. The operable activities include eating; walking; toileting; bathing; grooming; dressing; using a communication device; having a conversation; going to an appointment; using a household appliance; washing dishes; cooking or preparing a beverage; writing; reading; doing household chores independently; carrying or shopping.

The present invention relates to RNA therapy and, in particular, decreasing immunogenicity of RNA. Specifically, the present invention provides methods for decreasing immunogenicity of RNA, said methods comprising modifying the nucleotide sequence of the RNA by reducing the uridine (U) content, wherein said reduction of the U content comprises an elimination of U nucleosides from the nucleotide sequence of the RNA and / or a substitution of U nucleosides by nucleosides other than U in the nucleotide sequence of the RNA. Using RNA having decreased immunogenicity allows administration of RNA as a drug to a subject, e.g. in order to obtain expression of a pharmaceutically active peptide or protein, without eliciting an immune response which would interfere with therapeutic effectiveness of the RNA or induce adverse effects in the subject.

The present invention relates to RNA therapy and, in particular, decreasing immunogenicity of RNA. Specifically, the present invention provides methods for decreasing immunogenicity of RNA, said methods comprising modifying the nucleotide sequence of the RNA by reducing the uridine (U) content, wherein said reduction of the U content comprises an elimination of U nucleosides from the nucleotide sequence of the RNA and / or a substitution of U nucleosides by nucleosides other than U in the nucleotide sequence of the RNA. Using RNA having decreased immunogenicity allows administration of RNA as a drug to a subject, e.g. in order to obtain expression of a pharmaceutically active peptide or protein, without eliciting an immune response which would interfere with therapeutic effectiveness of the RNA or induce adverse effects in the subject.