573 results about "RNA molecule" patented technology

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 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.

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 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 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.

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 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 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.

The present disclosure provides methods of processing or analyzing a sample. A method for processing a sample may comprise hybridizing a probe molecule to a target region of a nucleic acid molecule (e.g., a ribonucleic acid (RNA) molecule), barcoding the probe-nucleic acid molecule complex, and performing extension, denaturation, and amplification processes. The nucleic acid molecule may be a nucleic acid molecule associated with CRISPR, (e.g., a guide RNA). A method for processing a sample may comprise hybridizing first and second probes to adjacent or non-adjacent target regions of a nucleic acid molecule (e.g., an RNA molecule such as a guide RNA molecule), linking the first and second probes to provide a probe-linked nucleic acid molecule, and barcoding the probe-linked nucleic acid molecule. One or more processes of the methods described herein may be performed within a partition, such as a droplet or well. One or more processes of the methods described herein may be performed on a cell, such as a permeabilized cell.

A phosphorothioate-containing RNA molecule that includes the nucleotide sequence: 5'-NCCCUGGUGGUCUAGUGGUUAGGAUUCGGCGC-3' (SEQ ID NO: 1), where N is uracil or thymine, is provided. The RNA molecule can include one or more phosphorothioate bonds between nucleic acid residues in one or more pairs (e.g., between nucleic acid residues in each pair) of consecutive nucleic acid residues within SEQ ID NO: 1. The RNA molecule and compositions thereof find use in treating muscle disorders, such as muscular dystrophy, heart conditions, such as heart failure or myocardial infarction, and / or conditions associated with inflammation and / or fibrosis.

The invention provides a kind of RNA polymerase variants and application thereof, the variants have improved catalytic activity compared with wild type T7RNA 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.

Provided are a replicable RNA molecule and uses thereof, the present invention relates to a replicable RNA molecule comprising, from the 5'end to the 3 'end, a 5' cap, a 5 'UTR, an open reading frame encoding an RNA replicase, a promoter, a sequence of interest, a 3' UTR, and a poly (A) tail wherein the RNA replicase is capable of amplifying the replicable RNA molecule and an RNA molecule containing the sequence of interest and the 3 'UTR wherein the RNA replicase is derived from the group consisting of the group consisting of the MosdPedras virus, MDPV, EVEV, Riogro virus, Mycovirus, Mycovirus, Mycovirus, Mycovirus, Mycovirus, Mycovirus, Mycovirus, Mycovirus, Mycovirus, Mycovirus, Mycovirus and Mycovirus. RnV, Muslim virus, MUCV, Highland J virus, PIXV, TROV, Cabassu virus, TONV, Bebaru virus, BEBV, Formun virus, GETV, or Nnumu virus, and NDUV can be used in the treatment of a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, a disease, and a disease.

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 in-situ sequencing method and an in-situ sequencing result region division method, and the in-situ sequencing method comprises the following steps: carrying out in-situ transcriptional library building on a sample, and carrying a coordinate tag and a UMI tag on each nucleic acid molecule of an obtained sequencing library; determining additional information of at least one part of the plurality of sequencing reads based on the comparison, the additional information comprising at least one of the following: corresponding genes, coordinates, UMI, and classification results (whether to belong to mitochondrial / nuclear conservative long non-coding / mature / immature / clipped / unclipped RNA molecules) of the sequencing reads; classifying the sequencing reads into a first sequencing read group and a second sequencing read group; obtaining a plurality of first high-density regions of the first sequencing read group and a plurality of second high-density regions of the second sequencing read group; the plurality of first and second high density regions are merged to construct a pseudo cell region.

The present disclosure provides methods of inducing an immune response against varicella zoster virus (VZV) in a human subject. The methods provided herein comprise administering to a human subject an immunogenic composition (e.g., a vaccine) comprising an RNA molecule formulated in a lipid nanoparticle. The disclosure also relates to the use of the immunogenic composition for the prevention or treatment of herpes zoster in a human subject.

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 a library construction method for UMI and Poly-A tail analysis and application of the library construction method. According to the invention, a novel library construction process is designed, a UMI + Poly-A tail tandem library process is established, all sequences of the Poly-A tail can be completely obtained, the method can be used for simultaneous sequencing analysis of UMI and Poly-A tail, absolute quantification can be carried out on original transcripts, the sequencing efficiency and precision are improved, short PCR products are connected in series, long fragments are formed, and the sequencing time is shortened. The advantages of long sequencing length and long reading length of Pacbio can be fully utilized, the most original RNA molecules are accurately backtracked and counted, and a real gene expression profile is obtained.

The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and / or NK cells. The methods can include inhibitory RNA molecule(s) and / or engineered signaling polypeptides that can include a lymphoproliferative element, and / or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and / or genetically modified T cells and / or NK cells are provided, such as, for example, those including riboswitches, MRB-CARS, recognition domains, and / or pH-modulating agents.

The present invention relates to compositions comprising an RNA molecule and pharmaceutical formulations comprising such compositions wherein the RNA molecule comprises an expression cassette encoding an immunogenic peptide comprising at least two fragments wherein each fragment comprises at least one epitope wherein the epitope is derived from an amino acid sequence encoded by human immunodeficiency virus (HIV). In addition, the present invention relates to a method of preventing or treating HIV.

A method for modifying a gene encoding or processed to a non-coding RNA molecule having no RNA silencing activity in a eukaryotic cell is disclosed, with the proviso that the eukaryotic cell is not a plant cell. The method comprises introducing a DNA editor into the eukaryotic cell, the DNA editor conferring a silence specificity of the non-coding RNA molecule for a target RNA of interest. Also disclosed is a method of modifying a gene for encoding or being processed into an RNA silencing molecule for a target RNA in a eukaryotic cell. Also disclosed are methods of preventing and treating various diseases, methods of inducing apoptosis, and methods of producing an eukaryotic non-human organism.

The invention provides an artificial non-coding RNA (Ribonucleic Acid) molecule, a DNA (Deoxyribose Nucleic Acid) molecule, a biological material and application of the artificial non-coding RNA molecule, the DNA molecule and the biological material in improving the carbon and nitrogen metabolism capability of rhizobium, and belongs to the technical field of genetic engineering, the nucleotide sequence of the artificial non-coding RNA molecule is as shown in SEQ ID NO.1, and the nucleotide sequence of the DNA molecule transcribing the artificial non-coding RNA molecule is as shown in SEQ ID NO.2; the invention also provides a recombinant vector and recombinant rhizobium with efficient carbon and nitrogen metabolism capability. According to the artificial non-coding RNA molecule and the recombinant expression vector constructed by using the RNA molecule, the utilization capacity of malic acid of the rhizobium can be remarkably improved, then the symbiotic nitrogen fixation capacity of the rhizobium is enhanced, the rhizobium and leguminous crops are symbiotic, and the yield and quality of the leguminous crops can be remarkably improved.