202 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 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 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 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 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 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 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.

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.

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 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 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.

Disclosed herein are a messenger RNA (mRNA) comprising an open reading frame (ORF) encoding a protein of interest, a heterologous 5' untranslated region (UTR) and / or a heterologous 3' UTR for highly expressing the protein of interest. A method for synthesizing the mRNA and uses of the mRNA are also provided.

The application provides a non-translated region sequence for regulating gene expression and a derivative thereof; and provides a series of 5'-UTR and 3'-UTR sequences designed and screened based on machine learning, genetic algorithm and / or data mining, which can significantly improve the expression amount and expression efficiency of target proteins in cells.

The present invention relates to an artificial nucleic acid molecule, a related product thereof and use thereof in the preparation of a medicament for DNA or RNA-based therapy, and to the use of a 3 '-untranslated region element (i.e., 3'-UTR) in said artificial nucleic acid molecule for translating a coding region of a nucleic acid molecule into a polypeptide or protein encoded by said coding region, and a method of obtaining RNA, polypeptide or protein. According to the present invention, the specific 3 '-UTR element capable of improving the RNA translation performance is included, such that the artificial nucleic acid molecule has the high RNA translation performance so as to provide the high potential value and the high application prospect in the development of the RNA treatment drug.

The present invention relates to a polynucleotide sequence comprising a 5' untranslated region (5' UTR), a messenger RNA (mRNA) coding region, and a 3' untranslated region (3' UTR), wherein the 5' UTR and / or 3' UTR are modified. The invention further encompasses compositions and methods for delivering the modified polynucleotide to a subject in need thereof for the treatment or prevention of neurological disorder or neurobiological psychotic disorders.

Described are nucleic acids that can be used for guide nucleic acid expression such as nucleic acids that comprise a polII promoter; an expression gene that is operably associated with the polII promoter; and a guide nucleic acid that is in the 3' untranslated region (UTR) of the expression gene. The expression gene may have a length of about 200, 225, 250, 275, 300, 325, or 350 nucleotides to about 375, 400, 425, 450, 475, 500, 525, 550, 575, or 600 nucleotides.

(1) An artificial nucleic acid molecule comprising (a) at least one of a 3'-untranslated region (3'UTR) element and / or (b) a 5'-untranslated region (5'UTR) element, and (2) a poly(A) tail is described. The artificial nucleic acid molecule may further comprise a polypeptide comprising a reverse transcriptase (RT) domain and optionally an endonuclease domain for genome modification. A system comprising the artificial nucleic acid molecule and a method of using the system are also described.

The present invention relates to the field of biomedicine technology, and specifically discloses an mRNA based on the CP protein gene of fish nervous necrosis virus, a vaccine, and a preparation method and application thereof. The present invention provides an mRNA of fish nervous necrosis virus, the nucleotide sequence of which is shown in SEQ ID NO: 1, and the structure includes a 5' untranslated region, a signal peptide sequence, an NNV virus antigen coding region, a 3' untranslated region and polyA. The mRNA vaccine contains the ORF sequence of the capsid protein CP gene that is resistant to NNV virus infection. The results of animal safety tests on the fish nervous necrosis virus mRNA vaccine prepared by the present invention show that the vaccine is safe and effective, and is convenient and simple to use clinically, and has broad application prospects in the prevention and control of viral nervous necrosis in marine cultured fish.

The invention relates to novel oligonucleotides and their use in inhibiting or reducing senescence. The oligonucleotides target specific sequences in the 3' untranslated region (UTR) of heterogeneous nuclear ribonucleoprotein D (HNRNPD) mRNA and blocks one or more inhibitory microRNA (miRNA) binding sites. This promotes the physiologically regulated expression of HNRNPD and reduces senescence.

The invention described here contains a nucleic acid expression cassette comprising a transcriptional regulatory region operably linked to a nucleic acid sequence encoding a FKRP, an RNA transcript comprising a modified 5′ and / or 3′ untranslated region (UTR) that will be utilized to treat a variety of FKRP-mediated diseases.

The application belongs to the technical field of animal genetic engineering, and particularly discloses a construction method of C1R gene humanized animal cells and animal models and application thereof. The construction method of the C1R gene humanized animal cells comprises the following steps: introducing a human C1R gene into non-human animal cells, so that the human C1R gene is expressed in the non-human animal cells to produce humanized C1R protein, and meanwhile, the expression of an endogenous C1ra gene in the non-human animal cells is reduced or eliminated. The application preferably adopts CRISPR / Cas9 gene editing technology to accurately insert a genomic sequence encoding a human C1R mature protein into a 2nd exon region of a mouse C1ra gene, while retaining a mouse source promoter, a 5' untranslated region (UTR) and a signal peptide sequence. A mouse cell or model capable of specifically interacting with an anti-human C1R antibody is successfully constructed.

The present disclosure relates to an mRNA molecule comprising a 3 '-untranslated region (3'-UTR) of a sense single-stranded RNA (+ ssRNA) of a virus, a coding sequence of a protein that is heterologous for the virus, and a 5 '-untranslated region (5'-UTR). In particular, the present disclosure relates to mRNA encoding a protein of interest but lacking a poly (A) tail. In addition, the present disclosure relates to such mRNA that allows the addition of an adenine homopolymer at its 3'end.

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 application relates to an mRNA untranslated region translation efficiency prediction method and device, computer equipment and a storage medium. The method comprises the following steps: extracting sequence features and structure features of an mRNA sequence to be predicted, the structure features being generated by encoding based on at least one of free energy change and secondary structure of the mRNA sequence to be predicted; inputting the sequence features and the structure features into a trained translation efficiency prediction model for prediction to obtain a translation efficiency prediction result of an untranslated region in the mRNA sequence to be predicted. The method can improve the accuracy of the mRNA untranslated region translation efficiency prediction result.

The application provides a novel IRES sequence and variants thereof, untranslated region sequences suitable for circular RNA. A circular RNA drug comprising the above IRES sequence, untranslated region sequence, and protein coding sequence is provided. The circular RNA drug platform of the application has high protein translation efficiency (particularly in immune cells), a compact sequence length, compatibility with a variety of protein sequences, and drugs based on the circular RNA platform exhibit good therapeutic effects in animal tumor models.

Provided are: a transmission ribonucleic acid which comprises a non-natural 3'non-translated region (3 'UTR) and has excellent activity for improving the synthesis yield of a transmission ribonucleic acid (mRNA) of a gene; a composition comprising the transmission ribonucleic acid; a composition for delivering the signaling ribonucleic acid or polypeptide to a subject comprising the signaling ribonucleic acid; and a desoxyribonucleic acid encoding the signaling ribonucleic acid.