689 results about "RNA molecule" patented technology

The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-freeze drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry 10 powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

The present disclosure describes improved LNP-based RNA vaccines, nucleobase editing systems, and therapeutics for use in treating and / or immunization against disease. In particular, the disclosure describes improved LNPs, including novel and improved ionizable lipids for making LNPs, that enhance the targeted delivery of LNP-based RNA vaccines and therapeutics based on linear and / or circular mRNAs. The improved LNPs protect linear and / or circular mRNA payloads from degradation and clearance while achieving targeted systemic or local delivery for use as enhanced vaccines and / or therapeutic agents.

The present disclosure describes improved LNP-based RNA vaccines, nucleobase editing systems, and therapeutics for use in treating and / or immunization against disease. In particular, the disclosure describes improved LNPs, including novel and improved ionizable lipids for making LNPs, that enhance the targeted delivery of LNP-based RNA vaccines and therapeutics based on linear and / or circular mRNAs. The improved LNPs protect linear and / or circular mRNA payloads from degradation and clearance while achieving targeted systemic or local delivery for use as enhanced vaccines and / or therapeutic agents.

Among other things, the present disclosure provides oligonucleotides, compositions and methods thereof that can bring about specific editing of a target adenosine in a target RNA molecule. Such oligonucleotides, compositions and methods are useful to treat, prevent, or ameliorate MECP2 associated disorders, diseases and syndromes that can benefit from adenosine modification.

This disclosure provides improved RNA molecules, including mRNA molecules that can be produced by in vitro transcription and are suitable for in vivo transfection using an appropriate delivery vehicle, such as a lipid nanoparticle (LNP) or targeted lipid nanoparticle (tLNP). The improved RNA include particular combinations of 5' untranslated region (UTR) and 3' UTR, particular 3' UTRs, or particular open reading frame sequences. Also provided herein are compositions of the LNP, or tLNP with an antibody as a targeting moiety, such as anti-CD8 antibodies that are used as targeting moiety.

The invention provides an enhancer RNA (Ribonucleic Acid) molecule MZGAe1 and application thereof, and relates to the technical field of biology. The invention provides an enhancer RNA (Ribonucleic Acid) molecule MZGAe1. The nucleotide sequence of the enhancer RNA molecule MZGAe1 is as shown in SEQ ID NO: 1; meanwhile, the invention further provides a specific sgRNA sequence for activating the molecule in a targeted manner and a recombinant vector of the specific sgRNA sequence. Expression of endogenous MZGAe1 of cells is specifically activated by adopting a CRISPR activation technology, and conversion of mouse embryonic stem cells to bicellular-like cells can be efficiently promoted. By providing a brand-new endogenous targeted MZGAe1 accurate activation tool, the efficient transformation of wild mouse embryonic stem cells to bicellular cells can be realized only under the condition of endogenous activation of single enhancer RNA molecule MZGAe1, the proportion is at least increased by 5%, the expression of a totipotent marker gene ZSCAN4 is activated, and the expression of the totipotent marker gene ZSCAN4 is promoted. And an efficient and specific brand-new research tool and scheme are provided for researching zygote genome activation, embryonic development early events and cell reprogramming.

The invention discloses a self-replicating RNA (Ribonucleic Acid) molecule, a porcine rotavirus RNA vaccine and application thereof, and relates to the technical field of vaccines. According to the present invention, the coding sequence of the porcine rotavirus G9P23 type VP4 protein is optimized, such that the fact that the saRNA prepared by using the nucleotide sequence represented by the SEQ ID NO: 10 can secrete the high porcine rotavirus G9P23 type VP4 protein antigen after the cell transfection is found; after the optimized porcine rotavirus G9P23 type VP4 protein is used for immunizing experimental animals, the level of neutralizing antibodies generated by the animals can be improved, and the challenge protection effect is enhanced. Therefore, the nucleic acid molecule provided by the invention can be used for developing drugs and vaccines for causing protective immune response in experimental animal bodies. Compared with a traditional vaccine, the vaccine provided by the invention has good immunogenicity and safety, and has a good application prospect.

Methods and compositions for modulating a target genome and stable integration of a transgene of interest into the genome of a cell are disclosed. Specifically, provided herein comprises compositions comprising an RNA molecule comprising a reverse complement sequence comprising an exogenous sequence and homology arms, an RNA molecule comprising an endonuclease, and one or more guide RNAs for specific genomic integration of the exogenous sequence.

This disclosure provides improved RNA molecules, including mRNA molecules that can be produced by in vitro transcription and are suitable for in vivo transfection using an appropriate delivery vehicle, such as a lipid nanoparticle (LNP) or targeted lipid nanoparticle (tLNP). The improved RNA include particular combinations of 5′ untranslated region (UTR) and 3′ UTR, particular 3′ UTRs, or particular open reading frame sequences. Also provided herein are compositions of the LNP, or tLNP with an antibody as a targeting moiety, such as anti-CD8 antibodies that are used as targeting moiety.

The present disclosure provides compositions and methods for the targeted modification of RNA molecules by RNA prime editing. The compositions and methods may be conducted invitro or in vivo within cells (e.g., human cells) for the therapeutic correction of disease-causing mutations and / or installation of motifs or mutations in RNA molecules of interest as a tool for scientific research. The disclosure provides compositions and methods for conducting RNA prime editing of a target RNA molecule (e.g., an RNA transcript) that enables the incorporation of one or more nucleotide changes and / or targeted mutagenesis of a target RNA molecule. The nucleotide change can include a single-nucleotide change, an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides a variety of configurations of the RNA prime editors each comprising a nucleic acid programmable RNA binding proteins (napRNAbp), such as Cas13, and an RNA-dependent RNA polymerase (RDRP), which are provided as fusion proteins or which can be separately provided in trans. The RNA prime editors are guided to a target RNA site by a guide RNA, which can be a rpegRNA that includes a template region for the synthesis of an RNA sequence to be installed on the RNA molecule attached to an available 3′ terminus. In others embodiments, the RNA template can be provided in trans.

Disclosed are compositions comprising a nucleic acid molecule. The nucleic acid molecule may encode an exonic sequence or portion thereof of a target ribonucleic acid (RNA) sequence. The nucleic acid molecule may further encode one or more stabilization domains. The one or more stabilization domains may be configured to reduce a cellular nuclease activity compared to a nucleic acid molecule that does not comprise the one or more stabilization domains.

The invention provides a method for delivering double-stranded RNA (Ribonucleic Acid) molecules into locusts through epidermis, a product and application. The method provided by the invention comprises the following steps: mixing double-stranded RNA molecules to be delivered with a polymer carrier as shown in a formula 1 to obtain a mixture of the double-stranded RNA molecules and the polymer carrier; adding a surfactant into the mixture of the double-stranded RNA molecules and the polymer carrier to obtain a delivery mixture; the delivery mixture is contacted with the epidermis of the locust, so that the double-stranded RNA molecule enters the locust body through the epidermis. According to the method provided by the invention, the double-stranded RNA molecules can penetrate through relatively thick epidermis to enter the locust body, so that the stability of the double-stranded RNA molecules in the locust body is improved, and efficient gene interference is realized. The method provided by the invention can be used for research of locust gene functions and application of RNA pesticides.

The present disclosure relates to isolated nucleic acid molecules comprising at least two double-stranded inhibitory ribonucleic acid (RNA) molecules adapted to silence the same or different genes by RNA interference to enhance silence, thereby modulating gene expression.

The invention provides a kind of RNA polymerase variants and application thereof, the variants have improved catalytic activity compared with wild type T7 RNA polymerase, and the capping rate of mRNA products in the in vitro transcription (co-transcription capping) process can be increased. In addition, the disclosure also provides a method for preparing RNA by using the variant, and by using the method to prepare RNA molecules, more capped mRNA can be obtained.

Methods and compositions for modulating a target genome and stable integration of a transgene of interest into the genome of a cell are disclosed. Specifically, provided herein comprises compositions comprising an RNA molecule comprising a reverse complement sequence comprising an exogenous sequence and homology arms, an RNA molecule comprising an endonuclease, and one or more guide RNAs for specific genomic integration of the exogenous sequence.

The present application relates to single-stranded or double-stranded interfering RNA molecules (e.g., siRNAs) that target the alpha synuclein (SNCA) gene. The interfering RNA molecule may contain a specific pattern of nucleoside modification and inter-nucleoside linkage modification as a pharmaceutical composition comprising the interfering RNA 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 also 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 synucleinopathies.

The present disclosure relates to methods of identifying RNA targets of RNA binding proteins. In aspects, the disclosure relates to a method of identifying RNA molecules bound by RNA binding proteins. Some embodiments of the present disclosure relate to a method that can definitively identify direct RNA-target interactions with targeted proteins without the requirement for immunoprecipitation or gel extraction. In some embodiments, the method may include combining multiple antibodies in the same sample.

The invention discloses dsRNA of a targeted potato beetle heat shock protein HSP70-KDa3 gene as well as a preparation method and application of the dsRNA of the targeted potato beetle heat shock protein HSP70-KDa3 gene. In order to solve the problems that an existing RNAi target gene is prone to off-target, poor in field stability and the like, the potato beetle heat shock protein gene LdHSP70-KDa3 serves as an RNA interference target for the first time, and a double-stranded RNA molecule shown as SEQ ID NO: 1 and a preparation method for preparing the double-stranded RNA are provided. Feeding experiments prove that the double-stranded RNA can efficiently silence target genes, the survival rate of potato beetle larvae is remarkably reduced, and feeding and growth development of the potato beetle larvae are inhibited. In addition, the invention further provides a biological preparation containing the double-stranded RNA and application of the biological preparation in prevention and treatment of potato beetles. The dsRNA targeting the HSP70-KDa3 gene provided by the invention has the characteristics of high efficiency, specificity, environmental friendliness and the like, and a new technical scheme is provided for green prevention and control of potato beetles.

The present invention relates to antisense oligonucleotides (AONs) that can mediate RNA editing by binding to a target RNA nucleic acid molecule, preferably an RNA transcript molecule, in a cell and recruiting an endogenous deaminating enzyme in the cell to deaminate a target adenosine in the target RNA molecule to an inosine. The target RNA molecule is a transcript molecule form the SLC10A1 gene that encodes the Na+ / Taurocholate Co-transporting Polypeptide (NTCP), and the target adenosine is the adenosine in the GAC codon coding for aspartic acid (D) at position 24 of the NTCP protein. The deamination of the adenosine changes the amino acid to a glycine (G). The RNA editing of the adenosine will result in a loss-of-function of the NTCP protein, which will result in lowered uptake of bile acids from the portal circulation into the liver, thereby lowering the risk of suffering from disorders related to bile accumulation in the liver.

96 New PCT-Patent Application based on EP 24 186 635.9 Insempra GmbH Vossius Ref.: AG4141 PCT S3 Abstract The present invention relates to a linear double-stranded deoxyribonucleic acid (dsDNA) molecule comprising one or more Tus protein (Tus) binding site(s) at the 5'-terminus, one or more Lac repressor protein (LacI) binding site(s) at the 3'-terminus, and a segment comprising a DNA sequence of interest (DOI) between said Tus binding site(s) and said LacI binding site(s). The present invention further relates to a non-naturally or naturally occurring RNA molecule as encoded by or transcribable / transcribed from the linear dsDNA molecule of the invention, and to an expression DNA cassette comprising a promoter, an RBS, a GOI encoding a POI, and one or more LacI binding site(s), wherein said expression cassette does not comprise a terminator sequence between the 3´ end of said GOI and said one or more LacI binding site(s). The present invention also relates to a non-naturally or naturally occurring RNA molecule as encoded by or transcribable / transcribed from said expression cassette. The present invention further relates to method of protecting a linear deoxyribonucleic acid (DNA) molecule from exonuclease degradation by adding one or more Tus binding site(s) at the first terminus of the DNA molecule and adding one or more LacI binding site(s) at the other terminus of the DNA molecule. The present invention further relates to a method of synthesizing a protein of interest (POI) in a cell- free protein synthesis (CFPS) reaction mixture by using the (ds)DNA and / or RNA molecules of the invention, and also to a cell-free biological system or CFPS reaction mixture comprising the (ds)DNA, expression cassette and / or RNA molecules of the invention.

Embodiments of the present disclosure include compositions and methods for conducting in situ hybridization reactions. In particular, the disclosure provides RNA blocking molecules that enhance the detection of target RNA molecules (e.g., mRNA molecules, micro RNA (miRNA) molecules, small non-coding RNA (sncRNA) molecules, PIWI interacting RNA (piRNA) molecules, and / or small interfering RNA (siRNA) molecules) by reducing the binding of a target probe to non-target RNA molecules in a sample.

The invention relates to the technical field of biology, in particular to a 5 'UTR sequence for promoting mRNA translation and application of the 5' UTR sequence. The invention provides a 5 'UTR sequence which comprises a nucleotide sequence as shown in any one of SEQ ID NO: 1-6 or a complementary sequence thereof, or a nucleotide sequence with at least 80% homology with the nucleotide sequence as shown in any one of SEQ ID NO: 1-6 or the complementary sequence thereof. The invention provides a brand new RNA molecule design scheme, and the advantage of optimizing translation is realized by reasonably optimizing the nucleic acid sequence of the functional region, so that the RNA molecule has wide application prospects in the fields of gene therapy, vaccine research and development and the like.

The current invention relates to ionizable lipid-like compound according to Formula (I) or pharmaceutically acceptable salt, tautomer, or stereoisomer thereof.The present invention also provides a lipid nanoparticle comprising an ionizable lipid-like compound according to Formula I and one or more RNA molecules, as well as a pharmaceutical composition or vaccine, comprising such lipid nanoparticles.

The invention relates to the technical field of genetic engineering, and particularly provides a multi-linked quality control product for quality control of a novel coronavirus nucleic acid detection laboratory and a preparation method of the multi-linked quality control product. The multi-linked quality control product is a multi-component composite system and is formed by mixing three substances, namely pseudovirus, target gene RNA (Ribonucleic Acid) molecules and internal standard plasmid DNA (Deoxyribose Nucleic Acid). Wherein the pseudovirus is pseudovirus particles of novel coronavirus ORF1ab gene RNA (Ribonucleic Acid) wrapped by a vesicular stomatitis virus vector and is used for monitoring virus nucleic acid extraction; the target gene RNA molecule is a novel coronavirus N gene RNA molecule and can monitor the reverse transcriptase activity; the internal standard plasmid is plasmid DNA of a human housekeeping gene RPP30, and whether inhibition or failure exists in an amplification link is monitored. According to the method, the whole process of nucleic acid extraction, reverse transcription and amplification is synchronously and hierarchically monitored, the monitoring blind area of a traditional single-component quality control product is solved, and the accuracy and efficiency of laboratory detection quality control are remarkably improved.

The invention provides a preparation method of dendritic mesoporous silicon bionic nanoparticles loaded with RNA (Ribonucleic Acid) molecules, which comprises the following steps: preparing dendritic mesoporous silicon nanoparticles DMSNs by adopting a double-phase layering method, dissolving a surfactant CTAC and a catalyst TEA in water to serve as a water phase solution, dissolving ethyl silicate TEOS in cyclohexane to serve as an oil phase, slowly dropwise adding the oil phase into the water phase, and reacting for 2-4 hours to obtain the dendritic mesoporous silicon bionic nanoparticles loaded with the RNA molecules. The DMSNs nanoparticles are obtained; amino groups are introduced to the surfaces of DMSNs through gamma-aminopropyltriethoxysilane APTES so as to enhance electrostatic attraction to nucleic acid, and after a surfactant template is removed, the DMSNs are mixed with RNA molecules in ribozyme-free water; meanwhile, a cytoplasmic membrane is harvested by using a hypotonic method, and the dendritic mesoporous silicon bionic nanoparticles loaded with the RNA molecules are prepared through ultrasonic treatment and polycarbonate film extrusion. The method is simple and convenient, and has a wide application prospect in RNA delivery.

The application discloses an exosome small non-coding RNA molecule marker and application thereof, and belongs to the field of tumor liquid biopsy and molecular diagnosis. The exosome small non-coding RNA molecule marker is at least one of tRNA-GlyGCC-5 and sRESE; the nucleotide sequence of the tRNA-GlyGCC-5 is shown as SEQ ID NO:1; and the nucleotide sequence of the sRESE is shown as SEQ ID NO:2. The sRESE in the application is a brand new small non-coding RNA sequence, and is first discovered by the inventor, which is important for the marker of esophageal cancer and the research on disease progression mechanism. The tumor diagnosis kit provided by the application, which comprises the exosome small non-coding RNA molecule marker, is a liquid diagnosis monitoring kit with non-invasiveness, high sensitivity, high specificity and applicability to general survey or screening.

Synthetic RNA molecules comprising at least two RNA-binding protein (RBP)-binding motifs, wherein the at least two RBP-binding motifs bind the same first RBP and comprise non-identical sequences are provided. Synthetic RNA molecules comprising an RBP-binding motif that binds two orthogonal RBPs, comprising at least three RBP-binding motifs for three orthogonal RBPs or comprising a first RBP-binding motif, a second RBP-binding motif, a regulatory element and an open reading frame wherein the first and second RBP-binding motifs cooperatively enhance translation of the open reading frame are also provided. Compositions, cells and methods of use or generating the synthetic RNA molecules are also provided.

A gene editing system comprising (a) a fusion polypeptide comprising an RNA-guided nuclease and a reverse transcriptase, or a nucleic acid encoding the fusion polypeptide, and (b) an RNA molecule comprising a guide RNA and a reverse transcription donor RNA, or a nucleic acid encoding the RNA molecule. Also provided herein are methods of using the gene editing system for modifying target genes of interest.