71 results about "Target mrna" patented technology

The invention discloses antisense oligonucleotides for reducing XDH gene expression in a targeted manner and application of the antisense oligonucleotides, and belongs to the technical field of biological medicines. The antisense oligonucleotide mediates the degradation of the target mRNA through an RNase H (RNase H) dependent cleavage mechanism, and the mRNA expression of the XDH gene is horizontally knocked down after transcription; the antisense oligonucleotide molecule has a specific nucleic acid sequence, is combined with chemical modification design, can specifically bind XDH mRNA molecules in a targeting manner, promote XDH mRNA degradation and inhibit XDH protein synthesis, so that the expression level of XDH in cells is reduced, uric acid synthesis is reduced, the purpose of reducing uric acid is finally achieved, and cell experiments and animal model tests show that the antisense oligonucleotide molecule has a good application prospect. The antisense oligonucleotide molecule disclosed by the invention has a good uric acid reducing effect, and is long in drug effect duration and high in drug safety.

The present application relates to the technical field of mRNA sequence evaluation, and discloses a kind of mRNA sequence safety evaluation method, device, electronic equipment and storage medium, the method comprises: obtaining target mRNA sequence;Extract the biophysical characteristics of target mRNA sequence;Biophysical characteristics include: primary structure characteristics, secondary structure characteristics and functional characteristics;Biophysical characteristics are input into the mRNA sequence safety evaluation model constructed in advance, and safety evaluation result is obtained.The primary structure characteristics, secondary structure characteristics and functional characteristics of mRNA sequence are considered as comprehensive factors and input into the mRNA sequence safety evaluation model, the internal correlation between sequence structure characteristics, spatial structure characteristics, translation function characteristics and safety can be accurately captured, and the accuracy and reliability of the model for mRNA sequence safety evaluation are effectively improved.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of micro-interfering ribonucleic acid (miRNA). The sequences of miRNA may be complementary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule and the miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a serotonin receptor, such as serotonin receptor 5HT1a, 5HT1b, 5HT1d, 5HT1e, 5HT1f, 5HT2a, 5HT2b, 5HT2c, 5HT3, 5HT4, 5HT6, or 5HT7.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of micro-interfering ribonucleic acid (miRNA). The miRNA may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for a target biomolecule and the miRNA can cause the target mRNA to be degraded or inactivated, decreasing the bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a complement or a factor. In some embodiments of the present disclosure, the target biomolecule is a complement such as complement C1q, complement C1r, complement C1s, complement C3 or complement C5. In some embodiments of the present disclosure, the target biomolecule is a factor such as Factor B, Factor D or Factor 10.

Modified multi-segment antisense oligonucleotides and methods for reducing expression of target mRNA, DNA, and proteins are provided. Such methods, oligonucleotides, and compositions may be used to treat, prevent, or ameliorate a disease or disorder.

This invention relates to the field of biomedical detection technology, and discloses a bitetrahedral framework nucleic acid TDN cascade amplification system and its application, including TDN-1 and TDN-2. TDN-1 has a hairpin H1 containing a fluorescent reporter group attached to its surface, and TDN-2 has a hairpin H2 attached to its surface. The sequences of H1 and H2 are designed to undergo an alternating hybridization chain reaction triggered by target mRNA. This scheme relies on the synergistic effect of TDN structural anchoring and precise hairpin probe sequence design to overcome the technical defects of traditional free HCR hairpins in living cells, such as poor stability, low reaction efficiency, and non-specific triggering, achieving more efficient and specific intracellular signal amplification. Furthermore, it enables highly specific and sensitive in-situ imaging and dynamic tracking of low-abundance mRNAs such as c-Myc in single living cells, effectively solving the problems of insufficient detection sensitivity and false positives caused by the inability of traditional detection methods to effectively enrich targets and the low efficiency and high background of traditional HCR and other signal amplification technologies in intracellular applications.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of micro-interfering ribonucleic acid (miRNA). The sequences of miRNA may be complementary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule and the miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a serotonin receptor, such as serotonin receptor 5HT1a, 5HT1b, 5HT1d, 5HT1e, 5HT1f, 5HT2a, 5HT2b, 5HT2c, 5HT3, 5HT4, 5HT6, or 5HT7.

The present disclosure relates to compositions that upregulate the production of one or more sequences of micro-interfering ribonucleic acid (miRNA). The sequences of miRNA may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule, and the miRNA may cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is an opioid receptor. In some embodiments of the present disclosure, the target biomolecule is one or more of the mu opioid receptor, the delta opioid receptor, the kappa opioid receptor and the nociceptin opioid receptor.

The embodiments of the present disclosure relate to one or more compositions or methods that upregulate the production of one or more sequences of micro-interfering ribonucleic acid (miRNA). The sequences of miRNA may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule, such as CXCR5. The miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA. Decreasing the bioavailability of the target biomolecule within a subject that is administered the one or more compositions may address the afflictions experienced by the subject due to expression of the target biomolecule.

A single-stranded oligonucleotide having a length of 16-30 nucleotides. The composition of the single-stranded oligonucleotide enables the single-stranded oligonucleotide to inhibit the expression of target mRNA by means of an RNAi mechanism. Each nucleotide in the single-stranded oligonucleotide is independently a modified or unmodified nucleotide, wherein at least one nucleotide in the single-stranded oligonucleotide is a nucleotide X; at least one nucleotide is a fluoro-modified nucleotide; and, in the 5' to 3' direction, the 13th nucleotide of the single-stranded oligonucleotide is a substituted alkoxy-modified nucleotide, the 14th nucleotide of the single-stranded oligonucleotide is a nucleotide X, and each of the 15th nucleotide and all subsequent nucleotides of the single-stranded oligonucleotide is independently a modified nucleotide. A double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate and a pharmaceutical composition.

Embodiments of the present disclosure relate to a composition that comprises a recombinant plasmid (RP) with a sequence of nucleic acids. The sequence comprise a start region, an end region and an insert positioned between the start region and the end region. The insert encodes for a sequence of micro interfering ribonucleic acid (miRNA) that may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule. The miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is an immune checkpoint protein.

The application discloses a PACE structure modified cap analog, which is based on the existing cap analog structure, has ribose bases or modified ribose bases at both ends, three ribose structures in the middle and a triphosphonate segment or a phosphonate segment connecting the ribose structures, and has one or more PACE structures or PACE derivative structures on the triphosphonate segment or the phosphonate segment, namely, (alkoxy)alkyl-COOH or a salt thereof with or without substitution on the triphosphonate or the phosphonate, so that the IVT yield and capping efficiency are improved, and the translation efficiency of the target mRNA is improved.

The present disclosure relates to oligonucleotides comprising lipophilic monomers and their use in non-hepatic delivery. Specifically, the present disclosure relates to an oligonucleotide comprising an antisense strand complementary to a target mRNA, a sense strand complementary to the antisense strand, and one or more nucleotides represented by Formula (I-1) or (I-2). The disclosure also relates to a pharmaceutical composition comprising the oligonucleotide, and a medical use of the oligonucleotide and / or the pharmaceutical composition.

The present invention discloses a lipid nanoparticle (LNP) and its application, comprising cationic ionisable lipids, auxiliary lipids, ligand-modified PEGylated lipids, and cholesterol. The auxiliary lipids and ligand-modified PEGylated lipids target receptors on the surface of liver sinusoidal endothelial cells (LSECs). The LNPs enhance LSEC-specific uptake through a targeted design involving the lipid-specific interaction pathway.

The present disclosure relates to the technical field of biological delivery, and discloses a linker with a specific structure, a compound including the linker, a method of preparing the compound, use of the linker, and a method of delivering oligonucleotides through the linker. The linker of the present disclosure may be linked to the oligonucleotides, and may be hydrolyzed to release the oligonucleotides linked thereto, and the oligonucleotides bind to the same or different positions of the same target mRNA, or the oligonucleotides bind to two or more target mRNAs.

Provided herein are nucleic acid agents that are or comprise one or more nucleic acid molecules, together comprising (a) a complementary element that hybridizes with a target mRNA; and (b) a poly(A) element. In some embodiments, the target mRNA is an mRNA of an active allele of a gene associated with a disorder associated with a decrease in the expression of a protein from the mRNA, wherein the disorder is a haploinsufficiency disorder.

A nucleoside phosphoramidite compound, the compound being a 2'-phosphoramidite group, 4'-modified TNA structured compound. The nucleoside phosphoramidite compound can be used to incorporate into the first and / or last and / or intermediate of an oligonucleotide such that the modified oligonucleotide hybridizes to a portion of a target mRNA, thereby causing a loss or down-regulation of normal function of the target mRNA.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of micro-interfering ribonucleic acid (miRNA). The sequences of miRNA may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule and the miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a serotonin receptor, such as serotonin receptor 5HT1a, 5HT1b, 5HT1d, 5HT1e, 5HT1f, 5HT2a, 5HT2b, 5HT2c, 5HT3, 5HT4, 5HT6, or 5HT7.

An antisense oligonucleotide targeting inhibin βE (INHβE) and the use thereof. The antisense oligonucleotide molecule has a length of 16-22 bases. The antisense oligonucleotide molecule can target mRNA and pre-mRNA sequences of INHβE and reduce the expression thereof. The antisense oligonucleotide molecule has the following uses: (1) in the preparation of a preparation for inhibiting the expression level of INHβE; or (2) in the treatment of diseases caused by hepatic steatosis and / or insulin resistance.

Disclosed in the present invention are a modified nucleoside and nucleoside monomer, an oligonucleotide containing the modified nucleoside monomer and the use thereof. According to the present invention, lipophilic / hydrophilic groups, fragments with a pharmacological activity and receptor-targeting properties, etc., are introduced to modify a nucleoside, thereby obtaining a modified nucleoside and a phosphoramidite monomer thereof. The modified nucleoside has significantly improved physicochemical properties and bioavailability. According to the present invention, the modified nucleoside is further incorporated into an oligonucleotide, such that the cellular free uptake efficiency of an oligonucleotide drug can be significantly enhanced, and a target mRNA can be silenced. The present invention holds promise for achieving efficient delivery of a modified nucleic acid drug to various organs and tissues for the treatment of relevant indications.

The invention relates to a method for screening Alzheimer's disease markers by using a bioinformatics technology and application of the Alzheimer's disease markers. Serum microRNA samples of Alzheimer's disease normal subjects (NC), mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients in an NCBI public database are analyzed, and a bioinformatics analysis method is adopted to systematically identify common miRNA which commonly presents differential expression at the early stage and the late stage of the disease, so that target mRNA of the common miRNA is predicted, and a regulatory network is constructed; and finally screening out specific miRNA closely associated with the key mRNA as a disease monitoring marker. The method breaks through the high-cost limitation of traditional dependence on high-throughput sequencing, realizes efficient and reliable screening and identification of disease molecular markers by deeply mining public data resources, provides a new molecular target and detection means for early diagnosis, illness monitoring and intervention treatment of Alzheimer's disease, and has a wide application prospect. The important clinical application value is realized.

The present invention relates to the use of small artificial RNA (hereafter referred to as "smartRNA") containing sequences creating secondary structure motifs similar to C / D box small nucleolar RNAs (snoRNAs), and antisense guide sequences, as a tool for targeted upregulation of protein expression. The smartRNAs assembles into a ribonucleoprotein (RNP) complex resulting in a smartRNP, increasing the 2´-O-methylation level of one or more adenosines of the polyA-tail of the target mRNA, thereby delaying deadenylation of the targeted mRNA, resulting in increased protein production.

The application belongs to the technical field of genetic engineering, and particularly relates to a CsECT protein related to the disease resistance of plants, a recombinant vector and application thereof. 6 The CsECT protein provided by the application is synthesized by the gene CsECT, and the gene CsECT is speculated to be an m A reader, which affects the metabolism of target mRNAs, improves the stability of disease resistance related target genes, promotes the expression of disease resistance genes, and further improves the disease resistance of plants. The results of the examples show that the CsECT gene is cloned to construct a CsECT transgenic citrus, the transgenic citrus overexpresses the CsECT gene, and the disease resistance of the citrus to bacterial wilt can be significantly improved, thereby improving the disease resistance of the citrus. It can be seen that the CsECT protein synthesized by the gene CsECT can improve the disease resistance of plants.

The invention discloses a method for producing mRNA (messenger ribonucleic acid) template plasmids by fermenting escherichia coli, which comprises the following steps: firstly, inoculating a recombinant escherichia coli seed solution into a basic culture medium, fermenting and culturing until the OD600 value is 18-22, and then continuously adding a fed-batch culture medium at the feeding rate of 11-23 mL / L / h, the seed culture medium contains 1-5 mmoL / L of metal ion chelating agent and 0.5-1.5 g / L of anhydrous magnesium sulfate, the carbon source of the basic culture medium is 15-25 g / L of glycerol, and the pH value of the basic culture medium is 7-8. The culture medium contains 3-21 mmoL / L of a metal ion chelating agent and 1.5-4.5 g / L of anhydrous magnesium sulfate, the carbon source of the fed-batch culture medium is 260-450 g / L of glycerol, and the metal ion chelating agent is preferably sodium citrate. The method optimizes and reduces the aggregate superhelix content of the mRNA template plasmid from the aspects of culture medium formula and culture condition, and is beneficial to large-scale production of high-quality target mRNA template plasmid.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of micro-interfering ribonucleic acid (miRNA). The sequences of miRNA may be complementary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule and the miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a serotonin receptor, such as serotonin receptor 5HT1a, 5HT1b, 5HT1d, 5HT1e, 5HT1f, 5HT2a, 5HT2b, 5HT2c, 5HT3, 5HT4, 5HT6, or 5HT7.

The present application relates to a kind of magnetic bead complex for enriching mRNA and its application, belong to biotechnology field.The present application provides a kind of magnetic bead complex for enriching mRNA, including magnetic bead, interval arm, primer and oligodT, wherein, primer is coupled on magnetic bead by interval arm, oligodT is connected by primer with interval arm, interval arm is C chain and / or base T, primer is used to amplify target mRNA and is combined on the cDNA of magnetic bead after reverse transcription, oligodT can be specifically combined with target mRNA;The magnetic bead complex for enriching mRNA is provided with interval arm between primer and magnetic bead, on the one hand, can reduce the steric effect when in situ cDNA pre-amplification, enhance the efficiency of amplification, on the other hand, interval arm makes mRNA enrichment using the magnetic bead complex, can be in the case of magnetic bead reverse transcription, while also can carry out PCR amplification reaction.

The application discloses a kind of metal ion adjuvant-doped spleen-targeted mRNA vaccine.The mRNA vaccine includes mRNA-encapsulated spleen-targeted lipid nanoparticles and metal ion adjuvant;The mRNA-encapsulated spleen-targeted lipid nanoparticles include spleen-targeted lipid nanoparticles and mRNA;The raw material of the spleen-targeted lipid nanoparticles includes ionizable lipid, auxiliary phospholipid, cholesterol, polyethylene glycol-lipid conjugate and targeting functional lipid (anionic lipid).The application introduces anionic lipid as the fifth component in traditional LNP components, effectively realizes spleen lymphoid organ targeting while using its electrostatic adsorption with adjuvant Mn 2+ Between more efficient encapsulation of adjuvant Mn 2+ , to achieve simultaneous delivery of antigen and adjuvant to antigen-presenting cells in the spleen, improve Mn 2+ Activate the immune efficiency of a specific site, enhance the effectiveness of mRNA vaccine and reduce "off-target" toxicity, and thus achieve the purpose of tumor treatment and prevention.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of micro-interfering ribonucleic acid (miRNA). The sequences of miRNA may be complementary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule and the miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a serotonin receptor, such as serotonin receptor 5HT1a, 5HT1b, 5HT1d, 5HT1e, 5HT1f, 5HT2a, 5HT2b, 5HT2c, 5HT3, 5HT4, 5HT6, or 5HT7.

The present disclosure provides single-stranded or double-stranded interfering RNA molecules (e.g., siRNAs) that exhibit improved gene silencing. The present disclosure provides siRNA molecules having a fixed nucleobase region. For example, the antisense strand of the siRNA molecule may have a nucleobase region containing one or more mismatches relative to a target mRNA molecule. Alternatively or additionally, the antisense strand may contain a nucleobase region having a sequence independent of the target mRNA. An immobilization region may be included within a protruding end region of the antisense strand. The siRNA molecule may contain a specific pattern of nucleoside modification and a nucleoside-to-nucleoside linkage modification, as a pharmaceutical composition comprising the siRNA molecule. The siRNA molecule may be a branched siRNA molecule, such as a two-branched, three-branched or four-branched siRNA molecule. The disclosed siRNA molecules may further be characterized by a 5 '-phosphorus stabilizing moiety and / or a hydrophobic moiety. In addition, the present disclosure provides methods for delivering siRNA molecules of the present disclosure to a subject, such as the central nervous system of a subject identified as having a neurodegenerative disease.