14 results about "Phosphodiester bond" patented technology

Provided herein is a particle made of a protein covalently bound to a prebiotic carbohydrate, thereby forming a conjugate, wherein at least two said conjugates are covalently crosslinked via their carbohydrate units (e.g. by a phospho-di-ester bond). The said particle may be used for selectively promoting probiotic bacteria growth in the colon and may be used to deliver additional probiotic growth factors, or other bioactives and drugs to the colon. Furthermore, provided herein are methods for preparing the particle, and for delivering a substance bound to, or entrapped within the particle, into the gastrointestinal tract of a subject in need thereof.

The invention belongs to the technical field of environmental functional materials and water pollution control, discloses a cerium monatomic nano-enzyme as well as a preparation method and application thereof, and effectively solves the problem that an existing advanced oxidation technology lacks specificity on ARGs degradation and the problems that a traditional nano-enzyme is non-selective in catalytic mechanism and undefined in active site structure. According to the cerium monatomic nano-enzyme, a metal organic framework UiO-67-N is used as a carrier, pore channels of the carrier are modified through a nitrogen-containing ligand 2, 2 '-bipyridine-5, 5'-dicarboxylic acid, anchoring sites of cerium monatomic are constructed, a monatomic active center with a Ce-N6 coordination structure is formed, and cerium stably exists in a material framework in an atomic-scale dispersion form. According to the method, efficient recognition and cutting of extracellular DNA phosphodiester bonds in a neutral water environment are achieved, ARGs structures are directly destroyed, horizontal transfer pathways of the ARGs structures are blocked, and an enzyme simulation catalysis tool is provided for precise blocking and controlling of the ARGs in a water body.

The invention provides oligonucleotide and / or oligonucleotide analogue molecules that are antagonists of a microRNA, preferably antagonists of human microRNAs hsa-miR-23b-3p and hsa-miR-218-5p, that comprise a mixture of phosphorothioate and phosphodiester linkages, and that are conjugated to at least one oleic acid molecule. Inhibiting these microRNAs allows to increase the endogenous levels of the corresponding proteins MBNL1 and / or MBNL2. The present invention further provides compositions comprising said oligonucleotides and / or oligonucleotide analogue molecules and their uses for the treatment and prevention of DM in a subject in need thereof.

This invention discloses a circular RNA agent targeting PCSK9 and its applications, relating to the field of biomedical technology. The circular RNA agent is a single-stranded closed-circular oligonucleotide containing an antisense sequence complementary to the transcription of the PCSK9 gene. It lacks free 5' and 3' ends, and does not contain overhangs, hairpin structures, or double-stranded regions. The molecules are linked by 3'-5' phosphodiester bonds. This circular RNA agent can be modified with GalNAc or prepared into pharmaceutical compositions for the treatment of diseases or conditions related to abnormal PCSK9 gene expression or activity. The circular RNA agent provided by this invention exhibits high stability, a long half-life, low immunogenicity, low modification toxicity, and high target gene inhibitory activity. It can significantly prolong the dosing interval, improve patient compliance, and provide a safer, longer-acting drug option for lipid-lowering therapy.

The present application relates to the technical field of biological medicine, and in particular to a synthesis method and application of circular shRNA with gene knockdown function. The present application provides a synthesis method of circular shRNA with gene knockdown function. The ends of linear shRNA are connected by 2', 5'-phosphodiester bond to form circular shRNA, which can improve the stability of delivery in the environment of exonuclease. Moreover, after entering the cell, the 2', 5'-phosphodiester bond can be cleaved by DBR1 (Debranching RNA Lariats 1), so as to obtain shRNA, which can play the gene knockdown function of shRNA and play the role of inhibiting gene expression. The present application provides a new direction for developing a new nucleic acid drug for knocking down gene expression, and has a broad application prospect.

Provided are methods for non-enzymatically synthesizing nucleic acids. The methods include submerging a first portion of the outer surface of a cylinder in a non-enzymatic nucleic acid synthesis reaction mixture. The reaction mixture has a pH of 4 or less and includes an organizing matrix reagent and monophosphate nucleotides. The methods further include rotating the cylinder about its axis of radial symmetry so that the first portion of the outer surface of the cylinder is no longer submerged in the reaction mixture, thereby providing a thin film of the reaction mixture on the first portion of the outer surface of the cylinder. The methods further include heating and drying the thin film to form phosphodiester bonds between the monophosphate nucleotides of the thin film. Also provided are devices that find use, e.g., in practicing the methods of the present disclosure.

The present disclosure relates to a delivery platform for payload-specific and efficient directing of stable RNAi agents to hepatocytes in a subject. The delivery platform disclosed herein includes a metabolically stable N-acetylgalactosamine (NAG or GalNAc) targeting ligand conjugated to one or more oligonucleotides by a metabolically stable bond that is more stable than a phosphodiester bond to facilitate delivery of oligonucleotide-based payloads to cells, including hepatocytes. Also described are pharmaceutical compositions comprising the metabolically stable RNAi agent conjugate delivery platform, as well as methods for treating various diseases and conditions in which a therapeutic payload is required to be delivered to hepatocytes.

The present disclosure relates to delivery platforms that specifically and efficiently direct stabilized RNAi agent payloads to hepatocytes in a subject, in vivo. The delivery platforms disclosed herein include metabolically stabilized N-Acetylgalactosamine (NAG or GalNAc) targeting ligands conjugated to one or more oligonucleotides through a metabolically stabilized linkage that is more stable than a phosphodiester linkage, to facilitate the delivery of the oligonucleotide-based payloads to cells, including to hepatocytes. Pharmaceutical compositions that include the metabolically stabilized RNAi agent conjugate delivery platform are also described, as well as methods of use for the treatment of various diseases and disorders where delivery of a therapeutic payload to a hepatocyte is desirable.

The invention provides a synthesis method of a single-chain aptamer and application of the single-chain aptamer in synthesis of a C5 complement inhibitor, and relates to the technical field of aptamer synthesis, the synthesis method comprises the following steps: cutting off the single-chain aptamer into two fragments, pairing the two fragments through complementary bases carried by the two fragments to form a double-chain secondary structure with a single gap, and under the enzymatic action, synthesizing the C5 complement inhibitor by using the double-chain secondary structure to obtain the C5 complement inhibitor. A phosphodiester bond is formed at a notch of the double-chain secondary structure to obtain a single-chain aptamer, and the base length ratio of the two fragments is (14-26): (25-13). The self-complementary nucleic acid fragment of the to-be-synthesized single-stranded aptamer is used as a substrate, specific connection is realized under the action of ligase, an exogenous template chain is not needed, and the final purity and yield of the single-stranded aptamer are improved. The technical problems that in the prior art, enzymatic connection of single-stranded oligonucleotides needs to depend on an exogenous template, so that an experimental system is complex, mismatching is likely to happen, and connection position errors are likely to happen are solved.

The present application relates to the field of nucleic acid detection, and particularly relates to a novel nucleic acid detection method based on CRISPR-Cas12. By introducing chemical modification (such as locked nucleic acid modification), the present application constructs a method for site-specific cleavage of specific phosphodiester bonds in single-stranded nucleic acid by Cas protein containing RuvC domain and a method for detecting target DNA in a sample to be tested, so as to realize site-specific cleavage and trigger signal cascade amplification, and then realize rapid and high-sensitivity detection of nucleic acid.

The invention discloses low-purine and high-flavor bone soup and a preparation method thereof. According to the method, part of purine is removed through deep blanching, a core technology of performing enzymolysis by adopting a compound enzyme preparation of acid protease, nuclease and aminopeptidase is adopted, and the acid protease preferentially hydrolyzes collagen and muscle protein networks wrapping nucleic acid under a set pH value, so that the accessibility of a nucleic acid substrate is remarkably improved; then, nuclease specifically hydrolyzes the exposed RNA and DNA phosphodiester bond to degrade the RNA and DNA phosphodiester bond into nucleoside and purine / pyrimidine bases, and deep and efficient removal of purine is achieved from the source. Meanwhile, exonuclease can immediately trim the tail end of a peptide chain generated by protease hydrolysis, and accumulation of hydrophobic short peptides with bitter taste is effectively prevented. The final product not only retains the inherent mellow bone fragrance of the bone soup, but also has the excellent sensory quality of prominent delicate flavor, harmonious taste and long aftertaste.

The disclosed invention relates to a complex molecule comprising a linear double-stranded DNA product with exonuclease resistance due to the presence of internal protected nucleotides, preferably phos

Provided herein are reactive aromatic molecules (e.g., substituted chrysene heterodimers) encodable as base-four sequences for the design and integrated synthesis of nucleic acids (e.g., DNA, RNA, hybrid DNA / RNA) and associated phospholipid bilayers (e.g., cellular membranes). For example, 3,6,9,12-tetrasubstituted chrysene is coupled with 6,12-disubstituted chrysene through π-electron stacking to form a base-four heterodimer. The orientation of the ring structure of the tetrasubstituted chrysene in this heterodimer comprises a base-two (binary) structure and the relative alignment of the ring structure of the disubstituted chrysene to the tetrasubstituted chrysene comprises a second independent base-two (binary) structure. This collectively results in a base-four (quaternary) complex composed of four independent reaction environments. Methods of forming the heterodimers (and conjugated systems) include coupling sidechains of ethoxylated alcohol by phosphorylation. This may result in phosphodiester linkages at the 6,12 positions and / or uncoupled phosphorylated sidechains of ethoxylated alcohol at the 3,9 positions of the reactive aromatic molecules. The uncoupled phosphorylated sidechains may polymerize with adjacent tetrasubstituted chrysene through phosphodiester linkages. Various methods for initiating a reaction (e.g., oxidative cleavage) within the assembly of these π-electron stacked heterodimers can be utilized to produce nucleic acid sequences from the stacked tetrasubstituted chrysenes along with an associated phospholipid structure from the coupled disubstituted chrysene. Also provided herein are encoding and decoding design relations that can be utilized to map the base-four substituted chrysene heterodimers to the base-four nucleic acids (e.g., DNA, RNA, hybrid DNA / RNA). The present disclosure also includes various methods of regulating the sequence of substituted heterodimers to produce a specific encoding type of nucleic acid (e.g., DNA, RNA, hybrid DNA / RNA) and direct the 5′-3′ polymerization direction. The present disclosure also includes polycyclic pharmaceutical molecular agents resultant from the structural correlations in deriving the base-four heterodimer for subsequent synthesis to a sequence of nucleic acids and phospholipids.