119 results about "Target mrna" patented technology

The invention discloses a method for producing mRNA (messenger ribonucleic acid) template plasmids by fermenting escherichia coli. When the recombinant escherichia coli is fermented and cultured, a seed solution of the recombinant escherichia coli is inoculated into a basic culture medium to be fermented and cultured until the OD600 value of fermentation liquor is 18-22, then a fed-batch culture medium is continuously added at the feeding rate of 5-15 mL / L / h to be subjected to continuous fed-batch fermentation culture, the basic culture medium contains 0.05-0.2 mmoL / L of ferric salt compound and 0.05-0.2 mmoL / L of copper chloride dihydrate, and the basic culture medium contains 0.05-0.2 mmoL / L of ferric salt compound and 0.05-0.2 mmoL / L of copper chloride dihydrate. The basal culture medium contains 10-15 g / L of copper chloride dihydrate and 100-300 mg / L of p-hydroxybenzoic acid, the carbon source of the basal culture medium contains 0.1-0.3 mmoL / L of a ferric salt compound, 0.1-0.3 mmoL / L of copper chloride dihydrate and 100-300 mg / L of p-hydroxybenzoic acid, the carbon source of the fed-batch culture medium contains 360-480 g / L of glycerol, and the ferric salt compound is one or more of ferrous citrate, ferric ammonium citrate or ferrous sulfate heptahydrate. According to the method, the yield and superhelix content of the mRNA template plasmids are improved by optimizing the culture medium formula and culture conditions, and large-scale production of the high-quality target mRNA template plasmids is facilitated.

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 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.

Compositions are provided for transient transcriptional modulation of genes through delivery of RNA molecules encoding site-specific DNA binding molecules linked to transcriptional modulation domains, as well as methods for treating or preventing a disease or disorder, including a cancer, infectious disease, or immunological disease.

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 invention relates to a system for monitoring mRNA m6A methylation in hepatic stellate cells based on a hybridization chain reaction and a detection method, and belongs to the technical field of analysis and detection. In order to solve the problem of poor sensitivity and detection precision in the prior art, the invention provides a system for monitoring mRNA m6A methylation in hepatic stellate cells based on hybridization chain reaction and a detection method, the method comprises the following steps: contacting a target mRNA m6A methylation sample to be detected with a group of probes comprising a probe a and a probe b; the probe b is connected to an anti-rabbit IgG antibody to form a probe b attached with the anti-rabbit IgG antibody; combining with a rabbit monoclonal anti-m6A antibody; the rabbit monoclonal anti-m6A antibody can be combined with a target mRNA m6A methylated sample to be detected; a hairpin probe H1 monomer and a hairpin probe H2 monomer are subjected to a hybridization chain reaction to form a polymer, and imaging detection is carried out. The method has the advantages of high detection sensitivity, high detection selectivity and strong intuition.

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.

The invention relates to the technical field of poultry breeding, and particularly provides a novel application of miR-17-5p in chicken follicular development. Experiments prove that the miR-17-5p can inhibit autophagy and apoptosis of chicken follicular granular cells, so that granular cell proliferation can be promoted by promoting expression of the miR-17-5p in the chicken follicular granular cells, development of chicken ovary follicles is further promoted, and atresia is prevented. The invention also discovers that downstream target mRNA of miR-17-5p is MAP3K5, and researches find that MAP3K5 can promote autophagy and apoptosis of chicken follicular granular cells. The discovery provides a new thought for targeting particle cells to regulate dynamic balance between autophagy and apoptosis of the cells so as to improve the poultry breeding efficiency, and also expands the functional cognition of the JNK / BCL2 pathway in poultry research.

Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and / or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases. Some aspects of this disclosure provide mRNA-sensing gRNAs that modulate the activity of RNA-programmable endonucleases based on the presence or absence of a target mRNA. Some aspects of this disclosure provide gRNAs that modulate the activity of an RNA-programmable endonuclease based on the presence or absence of an extended DNA (xDNA).

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.

Disclosed herein, are hammerhead ribozymes that bind to a target mRNA comprising a NUH ribozyme cleavage site that have enhanced turnover rates. Also described herein, are methods of administering hammerhead ribozymes that bind to a target mRNA comprising a NUH ribozyme cleavage site to treat eye diseases.

The invention provides a targeted mRNA delivery system of muscle tissues and / or muscle cells based on aptamer functionalized LNP (Apt-LNP), the delivery system can significantly improve mRNA transfection of the muscle tissues, and meanwhile, mRNA expression in main organs such as liver and spleen is greatly reduced. The expression intensity of muscle tissue in-situ mRNA is improved through modification of the aptamer, meanwhile, mRNA expression in main organs such as the liver and the spleen is greatly reduced, and side effects caused by off-target of mRNA infectious disease vaccines are expected to be avoided. The method is expected to be applied to the field of infectious disease mRNA vaccines The invention also provides a targeting mRNA delivery system of lymph node tissues and / or immune cells based on the aptamer functionalized LNP (Apt-LNP). Compared with an existing lymph node targeting system, the Apt-LNP modified by the aptamer not only can realize lymph node mRNA targeting, but also can further target immune cells, and is expected to be applied to the field of tumor mRNA vaccines to enhance the curative effect of tumor vaccines.

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.

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 application belongs to the technical field of biological medicine, and specifically discloses preparation and application of self-assembled glycopeptide nanoparticles for mRNA vaccine delivery, wherein the nanoparticles are formed by self-assembly of a glycopeptide carrier, mRNA and manganese ions. In the nanoparticle preparation process, the manganese ions are adsorbed onto tryptophan and histidine through metal chelation, and play an adjuvant role in activating the cGAS-STING pathway after administration. The nanoparticles can effectively adsorb mRNA, can stably exist for 4 weeks at 4 DEG C, protect mRNA from enzymatic degradation, promote intracellular mRNA internalization and lysosome escape, effectively transfect eGFP-mRNA and Fluc-mRNA in DC2.4 and BMDC cells, and effectively target mRNA delivery to lymph nodes, activate the cGAS-STING pathway, effectively activate the specific immune system in a B16F10-OVA prevention model, delay tumor growth, and prolong the survival cycle of mice.

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.

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 CXCR1. 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 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.