10 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 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.

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.