356 results about "Untranslated region" patented technology

The invention provides an artificial nucleic acid molecule which is used for improving the expression quantity of target amino acid, polypeptide or protein. The artificial nucleic acid molecule at least comprises a target 5'untranslated region (UTR), a target coding region (CDS) and a target 3 'untranslated region (UTR). Wherein the sequence of the target 5 'UTR is one of the following sequences: 5' UTR of a high-expression gene and a 5 'UTR variant of the high-expression gene. The sequence of the target 3 'UTR is one of the following sequences: 3' UTR of a high-expression gene and a 3 'UTR variant of the high-expression gene. Optionally, the artificial nucleic acid molecule may further comprise, for example, a 5 '-end cap structure (Cap), a PolyA tail. The 5 'UTR and the 3' UTR have regulating effects on translation and stability of nucleic acid molecules, so that the 5 'UTR, the 3' UTR and variants thereof are selected from high-expression genes, the nucleic acid molecules can be further stabilized and are not easy to degrade, and the amount of protein or polypeptide obtained by translation of the nucleic acid molecules can be increased. The invention also provides methods for making, delivering, and using such artificial nucleic acid molecules, as well as the use of the artificial nucleic acid molecules for the treatment and / or prevention of related diseases or disorders.

The invention provides an UTR element NHP1 as well as a construction method and application thereof, and relates to the technical field of mRNA. A 5 'UTR with a good expression effect is designed by integrating dominant sequences of a human high-expression gene and a pathogen natural UTR, a chimeric structure NHP1 with high ribosome load is predicted through a calculation model, a DNA sequence of the NHP1 is as shown in SEQ NO 1, and an RNA sequence of the NHP1 is as shown in SEQ NO 2; an EGFP report system is adopted on the DNA level to rapidly screen UTR; the translation efficiency is quantitatively evaluated on the RNA level through luciferase mRNA (N1-methyl pseudouridine modification); and the particle size is controlled by a microfluidic technology, so that the optimized UTR-mRNA is efficiently expressed after being delivered.

The invention discloses polynucleotide, a pharmaceutical composition and application of the polynucleotide. In the application, a plurality of polynucleotide sequences targeting the 3'untranslated region of the nuclear fiber layer protein A mutant mRNA are newly designed, the expression level of the nuclear fiber layer protein A mutant (such as premature protein) can be reduced in the Lamin AmRNA stage, and meanwhile, the normal transcription of Lamin C is not influenced, so that the toxic and side effects are lower; the compound has a wide prospect in the aspect of preventing or treating diseases (especially progeria) related to mutation of the nuclear fiber layer protein A.

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.

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 embodiment of the invention discloses an mRNA sequence generation method and device, a model training method and device and electronic equipment. The method comprises the steps that a target protein sequence, a target species text corresponding to the target protein sequence and target translation efficiency corresponding to the target protein sequence are obtained; determining a first target embedding corresponding to the target species text, determining a second target embedding corresponding to the target protein sequence, and determining a third target embedding corresponding to the target translation efficiency; splicing the first target embedding, the second target embedding and the third target embedding to obtain a fourth target embedding; a sequence generation model is called to map the fourth target embedding, a target mRNA sequence is generated, and the target mRNA sequence comprises a first coding region, a first untranslated region and a second untranslated region; according to the embodiment of the invention, the accurate and complete target mRNA sequence can be obtained, the application effect of the target mRNA sequence can be improved, and the method can be widely applied to scenes such as cloud technology, artificial intelligence and smart medical treatment.

The present disclosure, in some aspects, relates to antisense oligonucleotides (ASO) for use in the prevention or treatment of a disease or a condition associated with low- density lipoprotein (LDL) in a subject. In some embodiments, the ASO effects site-directed adenosine-to-inosine (A-to-l) editing of a target adenosine in a target RNA sequence derived from a sequence of an endogenous low-density lipoprotein receptor (LDLR) gene such that: a) the modified LDLR protein has: (i) reduced binding to the inducible degrader of the LDLR protein (IDOL); (ii) increased stability; (iii) improved resistance to IDOL-mediated degradation; (iv) increased LDLR protein expression; and / or (v) increased activity or function to take up LDL; and / or b) editing of the 3'-untranslated region (UTR) of the target RNA leads to an increase in LDLR protein expression and / or stability.

The invention relates to the technical field of molecular biology and plant biology, and provides a 5 'UTR element and application thereof in improving the expression quantity of a plant target gene. Wherein the nucleotide sequence of the 5 'UTR is as shown in SEQ ID NO. 1. By introducing the specific nucleotide sequence, the structure and function of the 5 'UTR are optimized, and the stability of the target transcript mRNA can be promoted, so that the capability of translating the mRNA into the protein is improved. The method not only improves the expression level of the target gene, but also provides a new translation regulation strategy for plant genetic engineering. Through the innovative method, more efficient target gene expression can be realized in plants, and the method has important scientific and application values.

The invention provides a novel IRES sequence suitable for circular RNA and a variant and an untranslated region sequence of the IRES sequence. The invention provides a circular RNA drug containing the IRES sequence, the untranslated region sequence and the protein coding sequence. The circular RNA drug platform has efficient protein translation ability (especially in immune cells), simplified sequence length and compatibility to various protein sequences, and the drug based on the circular RNA platform shows a good treatment effect in an animal tumor model.

The present disclosure, among other things, provides machine-learning technologies for identifying and localizing particular genomic elements (e.g., gene elements and / or regulatory elements) within nucleotide sequences, such as DNA and / or RNA sequences. In certain embodiments, similar to the manner in which image processing methods can be used to localize particular objects in images at pixel level resolution, referred to as “segmentation,” systems and methods of the present disclosure predict presence and locations of certain genomic elements within nucleotide sequences, thereby “segmenting” nucleotide sequences. Accordingly, genomic element segmentation technologies described herein may be used to generate annotations that identify and label portions of nucleotide sequences according to their predicted (e.g., via machine learning models described herein) function—e.g., as protein-coding genes, untranslated regions, splice sites, promotors, enhancers, etc. Among other things, these genomic annotations may be used to inform underlying biological processes driving diseases and facilitate development of new therapies.

The present invention relates to a gene construct for expressing an mRNA, and a pharmaceutical composition, a vaccine composition, and a gene therapy composition, each comprising the gene construct. More specifically, the present invention relates to a gene construct including a coronavirus (SARS-COV-2: Severe acute respiratory syndrome coronavirus 2)-derived 5′ untranslated region (UTR) and / or 3′ untranslated region (UTR), and a pharmaceutical composition, a vaccine composition, and a gene therapy composition, each comprising the gene construct.

The invention discloses a modified 5 'UTR (Untranslated Region), mRNA (messenger Ribonucleic Acid) containing the modified 5' UTR and application of the modified 5 'UTR.

The present invention is inter alia directed to artificial nucleic acid constructs, preferably RNA, comprising at least one coding sequence encoding a RUNX3 transcription factor or a fragment or variant thereof, wherein the nucleic acid preferably comprises at least one heterologous untranslated region (UTR). Further provided are pharmaceutical compositions comprising the nucleic acid, preferably formulated in polyethylene glycol / peptide polymers, polymeric carriers, or lipid-based carriers. Also provided are methods of treating or preventing disorders, diseases, or conditions, and medical uses, in particular ocular disorders, diseases, or conditions such as proliferative vitreoretinopathy (PVR) or epiretinal membranes (EPR), using the RUNX3 encoding nucleic acids described herein.

The invention discloses a 5 'UTR library, a recombinant expression vector and a genetically engineered bacterium for improving the yield of folamin in pathogenic bacterium Badei and application of the 5' UTR library and the genetically engineered bacterium, and belongs to the technical field of microbial genetic engineering. The method comprises the following steps: designing an SD region based on a 16S rRNA (ribosomal Ribonucleic Acid) 3'end complementary sequence of a Buddei pathogenic bacterium XBD101 serving as an original strain, regulating and controlling the number of bases between the SD sequence and an initiation codon AUG and optimizing an UTR secondary structure to construct a library containing 14 UTR sequences, and replacing three sequences N4A, N7A and N18A with the strongest translation ability in the library to the UTR region of a folamin synthesis key gene fclC, so as to obtain the folamin peptide. And finally, the capacity upgrading of the folamin chassis strain is realized, and an important support is provided for the industrial production of agricultural antibiotics.

The invention provides an mRNA sequence optimization method and device, an mRNA molecule, a pharmaceutical composition and application, and relates to the technical field of artificial intelligence, in particular to the technical field of biological calculation and the like. The mRNA sequence optimization method comprises: obtaining a first mRNA sequence for synthesizing a target protein, the first mRNA sequence comprising a 5'untranslated region sequence and a coding region sequence; and adjusting the 5'untranslated region sequence and the coding region sequence with the goal of maximizing a first score of the first mRNA sequence to obtain an optimized second mRNA sequence for synthesizing the target protein, the first score reflecting at least one of the following indicators of the first mRNA sequence: translation initiation efficiency, codon adaptability index and minimum free energy.

The invention belongs to the technical field of medicines, and provides a method for screening a mutant strain and a high-virulence Seneca virus A mutant strain. The method for promoting Senecavirus A mutation provided by the invention comprises the following steps: inserting an RNAi target sequence between 3Dpol and a 3'untranslated region of an SVA starting strain; the target sequence of the RNAi contains a complementary sequence of an endogenous sequence of the miRNA. According to the research, mutagenesis is carried out on SVA by constructing a high RNAi pressure system, and a method for screening the mutant strain SVA is carried out by simulating an antiviral RNAi mechanism in a host, so that a natural evolution process of the virus is better met, a large number of stably inherited mutant strains can be obtained, and an efficient research and development means is provided for vaccine research and development aiming at the virus.

The present invention is a capped RNA which has a translated region beginning with a start codon and encoding a protein and an upstream region upstream of the start codon, and a branch part having a cap structure. This branch part preferably has at least one structure of the following (a) to (c): (a) a capped probe having a sequence complementary to a sequence of a part or all of the untranslated region and having the cap structure is hybridized to the untranslated region; (b) a branched chain branching from the middle of a main chain constituting the RNA is provided in a part of the untranslated region and the cap structure is provided in the branched chain; and (c) the RNA has a branch structure in which the 51 end of a main chain of the untranslated region is branched into two or more branches, the cap structure being provided in each branch.

The invention provides a small nucleic acid composition, application of the small nucleic acid composition in preparation of a medicine and a product, and belongs to the technical field of biological medicine. The invention designs a small nucleic acid composition ASO133 / 7 / 142 / 30 containing four corresponding antisense oligonucleotide fragments aiming at four regions of miR-133, let-7, miR-142-3p and miR-30 seed sequences contained in a 3 '-terminal untranslated region sequence of ATP2A2 mRNA (messenger ribonucleic acid), and the small nucleic acid composition ASO133 / 7 / 142 / 30 has a nucleotide sequence as shown in SEQ ID NO. 1. By adopting the small nucleic acid composition provided by the invention, the expression level of ATP2A2 in HL-1 cells can be increased, and the expression level of ATP2A2 in heart tissues can be remarkably improved.

The invention discloses a recombinant escherichia coli strain, a preparation method and application thereof, and a synthesis method of oryzanol A, and relates to the technical field of bioengineering. The recombinant escherichia coli strain takes E.coli BL21 (DE3) as a chassis cell, and is modified as follows: (a) knockout of a gene pfkA; or, the gene pfkA is knocked out, and an untranslated region of the 5'end of the gltA gene is mutated from the sequence as shown in SEQ ID NO: 1 to the sequence as shown in SEQ ID NO: 2; and (b) inserting exogenous genes agmA, agmB, agmC, agmE and agmF, so as to obtain the gene. The recombinant Escherichia coli strain is high in growth speed and short in fermentation period (within 72 hours), a culture medium which is cheap and easy to obtain can be adopted, and compared with an existing Escherichia coli system, the fermentation yield of oryzanol A is obviously increased.

The invention relates to the technical field of biological medicines, and particularly discloses mRNA based on a fish nervous necrosis virus CP protein gene, a vaccine and a preparation method and application of the mRNA. The invention provides mRNA (messenger Ribonucleic Acid) of a fish nervous necrosis virus, which has a nucleotide sequence as shown in SEQ ID NO: 1 and structurally comprises a 5'end untranslated region, a signal peptide sequence, an NNV (Neuronecrosis Virus) antigen coding region, a 3 'end untranslated region and polyA. The mRNA vaccine contains an ORF sequence of a capsid protein CP gene capable of resisting NNV virus infection. Animal safety test results of the fish nervous necrosis virus mRNA vaccine prepared by the invention show that the vaccine is safe, effective and convenient and simple in clinical use, and has a wide application prospect in the aspect of prevention and control of viral nervous necrosis of mariculture fishes.

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 relates to the technical field of solid tumor immunotherapy, in particular to an IL-2mRNA multichannel delivery method for solid tumor immunotherapy, which comprises the following steps: designing a DNA template, using a plasmid containing an IL-2 gene sequence such as human IL-2cDNA, adding a T7 promoter, a 5'untranslated region UTR and a 3 'UTR at two ends to enhance translation efficiency, carrying out in-vitro transcription through T7 RNA polymerase, and carrying out in-vitro transcription through T7 RNA polymerase. And adding a 5 '-end cap analogue such as CleanCapAG to realize co-transcription cap adding, and then preparing lipid nanoparticle LNP encapsulation and carrying out surface modification. According to the IL-2mRNA multi-channel delivery method for solid tumor immunotherapy, through multi-channel delivery design, targeting optimization and combined treatment cooperation, the toxicity problem of a traditional IL-2 therapy and the drug resistance of MHC-I defective tumors are remarkably solved, meanwhile, efficient conversion is achieved through existing equipment, IL-2 expression can be accurately regulated and controlled, the immune microenvironment can be remodeled, and the immunotherapy effect is good. Meanwhile, the system is compatible with various treatment means such as chemotherapy, radiotherapy and immune checkpoint inhibitors.

To provide genome editing systems and related methods which allow for treatment of Hyper IgM Syndrome, a group of disorders characterized by defective CD40 signaling.SOLUTION: Provided herein is an isolated oligonucleotide donor template which comprises, from 5' to 3', A1-N-UTR-pA-A2, where A1 is a homology arm that is substantially identical to a first homology arm of a target CD40L nucleic acid; N is a cargo comprising one or more of exons 2-5 of a CD40L gene; UTR is a CD40L 3' untranslated region (UTR); pA is a polyA tail; and A2 is a homology arm that is substantially identical to a second homology arm of the target CD40L nucleic acid.SELECTED DRAWING: None

A method for predicting translation efficiency of an mRNA vaccine comprises the steps in which: an analysis device receives sequence information of a target mRNA vaccine; the analysis device extracts, from the sequence information, an input sequence including a 25 nt sequence to which a primer binds in a 5' untranslated region (UTR), a 50 nt sequence of the 5' UTR immediately before a coding sequence (CDS) site, and a 30 nt sequence after a start codon of a coding region; the analysis device calculates secondary structure information for the input sequence; and the analysis device inputs the input sequence and the secondary structure information into a pre-trained deep learning model so as to predict the translation efficiency of the corresponding mRNA vaccine.

The invention belongs to the technical field of biological medicines, and relates to application of LSR, LncRNA-LSR-AS1 or targeted siRNA in prevention and / or treatment of hyperlipidemia or related diseases thereof. The invention finds that the overexpression of the LSR gene shows a remarkable lipid-lowering effect in various hyperlipidemia models; the long-chain non-coding RNA (LncRNA-LSR-AS1) is specifically combined with a 3 'UTR (Untranslated Region) region of the LSR mRNA to negatively regulate the expression of the LSR gene; the targeting siRNA designed by aiming at the LncRNA-LSR-AS1 can be used for effectively inhibiting the expression of the LncRNA-LSR-AS1 and relieving the inhibiting effect of the LncRNA-LSR-AS1 on the LSR, so that the expression of the LSR is promoted. Effective intervention on hyperlipidemia can be achieved aiming at the target spots, the effects do not depend on an LDLR channel, and unique value is achieved for familial hypercholesterolemia with the poor PCSK9 inhibitor curative effect.

The present invention is a capped RNA which has a translation region starting from an initiation codon and encoding a protein, and an upstream region on the upstream side of the initiation codon, and which comprises a branch having a cap structure. It is preferable that the branch section has at least one of the following structures (a) to (c). (a) a capped probe having a sequence complementary to some or all of the sequences of the untranslated region and having a cap structure hybridizes to the untranslated region; (b) a branch that branches from the midway of the main chain constituting the RNA is provided in a part of the untranslated region, and a cap structure is provided in the branch; (c) The 5'end of the main chain of the untranslated region has a branch structure divided into two or more branches, and each branch is provided with a cap structure.

The invention discloses a 5 'UTR sequence and application thereof in improving mRNA translation efficiency, and belongs to the technical field of biology, the designed 5' UTR sequence has an excellent mRNA expression promoting function, and compared with a common HBA1 gene 5 'UTR, the FLuc mRNA expression level fused with the 5' UTR can be improved to 2-3.5 times.

The present invention relates to: a recombinant RNA molecule having improved expression efficiency of a target protein; and a DNA molecule encoding same. The present invention is based on the discovery of five 5' UTR sequences derived from F2, F9, CFHR3, MBL2, and C3 genes as optimal heterologous 5' UTR sequences that commonly increase protein expression with the greatest efficiency in various tissues in vivo, and these UTRs showed a protein expression increase equivalent to or up to 2 times greater than 5' UTR applied to mRNA vaccines that are currently available commercially. Accordingly, the present invention can be effectively used as an excellent nucleic acid therapeutic composition capable of stably and systemically producing a therapeutically effective amount of a pharmacological protein in the body of a patient.

The invention provides a 5 'UTR (Untranslated Region) element for improving protein expression quantity and application of the 5' UTR element, and belongs to the technical field of biology. The sequence of the 5 'UTR element is shown as SEQ ID NO.1. Modified mRNA is obtained by adding the 5' UTR element between an initiation codon of unmodified mRNA and 5 'UTR. Compared with the unmodified mRNA, the target protein expression quantity of the modified mRNA is remarkably improved, and meanwhile, the 5' UTR element is good in universality and suitable for improving the expression quantity of most mRNA, so that the 5 'UTR element has a good application prospect.

The present disclosure is generally related to the fields of microbial host cells, molecular biology, protein engineering, fermentation, protein production, and the like. Certain aspects of the disclosure are related to novel promoter and 5′-untranslated region a nucleic acid (DNA) sequences.