408 results about "Messenger ribonucleic acid" patented technology

The invention provides an application of a turnip crinkling virus P8 in inhibiting RNA silencing, and the nucleotide sequence of the P8 gene is as shown in SEQ ID NO: 1. Researches find that P8 has a silent inhibition function and can inhibit mRNA (messenger ribonucleic acid) of GFP (green fluorescent protein) from being degraded, so that the expression quantity of GFP protein is increased; in addition, it is found that the P8 can also increase the number of particles of an arabidopsis thaliana mRNA degradation pathway Procness body (a compound formed by interaction of Dcp1 protein and Dcp2 protein), and research results lay a foundation for clarification of P8 functions.

The invention discloses a high-pathogenicity porcine reproductive and respiratory syndrome virus mRNA vaccine composition and application thereof. The vaccine composition is selected from any one of the following combinations: (1) an mRNA vaccine composition consisting of a PRRSV GP3 mRNA (messenger ribonucleic acid), a PRRSV GP4 mRNA (messenger ribonucleic acid) and a PRRSV GP5 mRNA (messenger ribonucleic acid); or (2) an mRNA vaccine composition consisting of a PRRSV GP5 mRNA, a PRRSV membrane protein (M) mRNA and a PRRSV nucleocapsid protein (N) mRNA. According to the invention, a high-pathogenicity PRRSV JX-A1 strain is used as a template, and mRNAs capable of synthesizing a plurality of fusion proteins GP345, GP5M and GP5MN and single structural proteins GP3, GP4, GP5, M and N are respectively constructed. After liposome encapsulation, mice are inoculated for immunological evaluation, and results show that humoral immunity and cellular immunity levels of a single mRNA-LNPs mixed group are higher than those of recombinant mRNA-LNPs, and GP5 + M + N and GP3 + 4 + 5 have relatively best effects. The invention provides a new technical means for preventing PRRSV (Porcine Reproductive and Respiratory Syndrome Virus).

The invention relates to the technical field of biological information, in particular to a translation efficiency prediction method, a screening method, a model training method and electronic equipment. The translation efficiency prediction method is realized based on a translation efficiency prediction model, and the translation efficiency prediction model comprises an embedding module, a coding module and a prediction module. The method comprises the following steps: acquiring sequence data of messenger ribonucleic acid; extracting features of the sequence data through the embedding module to obtain feature representation of messenger ribonucleic acid; the feature representation is input into the coding module, the input feature representation is subjected to convolution processing through the coding module, a convolution result is coded based on an attention mechanism, and the updated feature representation is output according to a coding result; and performing translation efficiency prediction on the updated feature representation through the prediction module to obtain a translation efficiency prediction result. According to the embodiment of the invention, the translation efficiency of the messenger ribonucleic acid can be accurately predicted with high throughput, the screening efficiency is improved, and the screening cost is reduced.

The invention discloses a PEI and targeting peptide modified magnetic nano-carrier and a preparation method and application thereof. The nano-carrier is regular in morphology and uniform in particle size and has good crystallinity and magnetic performance. E5 polypeptide and RGD cyclic peptide on the surface of the nano-carrier are respectively combined with CXCR4 protein and integrin on the surface of a tumor cell, and the nano-carrier and CXCR4 are internalized into lysosome through an integrin-mediated way, so that the target protein CXCR4 is degraded. The PEI in the nano-carrier can load and deliver siRNA into tumor cells to silence the expression of CXCR4 mRNA (messenger Ribonucleic Acid). Through nucleic acid delivery and a protein targeted degradation strategy, the CXCR4 level of tumor cells is jointly reduced, the migration ability of the tumor cells is inhibited, and meanwhile, the anti-tumor effect of M1 type polarization of macrophages is activated.

The invention provides an application of an AC2 gene and the like in improving the expression quantity of GFP (Green Fluorescent Protein) and / or inhibiting degradation of an mRNA (Messenger Ribonucleic Acid) attenuated substrate taking the GFP as a reporter gene. Researches find that AC2 has an mRNA decay inhibition function, can inhibit degradation of a nonsense-mediated mRNA decay substrate taking GFP as a reporter gene and degradation of an endogenous nonsense-mediated mRNA decay substrate of arabidopsis thaliana, can improve the expression quantity of mRNA of AT1G0106020, RPS6, SMG7, AT5G35490, AT5G64430, AT1G36730 and the like, can reduce the expression quantity of AT1G72450 and AT2G400, has interaction with Dcp1 and Dcp2, and can be used for inhibiting the expression quantity of mRNA of AT1G0106020, RPS6, SMG7, AT5G35490, AT5G6430, AT1G36730 and the like. The growth ability of the yeast in an auxotroph culture medium can be improved, the expression level of Dcp1 can be reduced, and a research result lays a foundation for clarification of AC2 functions.

The nucleic acid composition containing the coded collagen is characterized in that the nucleic acid composition comprises mRNA (messenger ribonucleic acid) of the coded collagen.

The invention relates to a mutant of an RSV pre-fusion conformation F protein, the mutant comprises amino acid mutation relative to an amino acid sequence of a wild type RSV F protein, the amino acid mutation is that amino acids at positions 392 and 493 or near the 493 are substituted by C, and a disulfide bond is formed between mutated positions 392C and 493C or near the 493C. The invention also provides a related DNA (deoxyribonucleic acid) coding sequence, a recombinant plasmid, an mRNA (messenger ribonucleic acid) sequence and a corresponding RSV vaccine. By introducing disulfide bonds at proper positions and combining with cavity filling, electrostatic mutation, proline mutation and the like, the expression and stability of the F protein with conformations before and after fusion and trimerization conformations are remarkably improved, and the F protein is remarkably inhibited from being converted into conformations after fusion. The mutant is also applied to preparation of RSV vaccines and detection of respiratory syncytial virus infection.

The invention discloses an engineered bionic nucleic acid nano-vesicle as well as a preparation method and application thereof, relates to the technical field of nano biomedicine, and aims at solving the problems that in-vivo targeting efficiency and immunogenicity of a traditional cationic lipid nano-carrier are limited due to deletion and cleavage obstacles of GSDMD expression in tumor cells. The technical key point of the invention is as follows: the engineered bionic nucleic acid nano-vesicle is provided and is prepared by wrapping a cationic lipid nucleic acid drug with an exosome derived from engineered macrophages; wherein the exosome from the engineered macrophage is the exosome from the macrophage with high expression of PD1, which is as shown in SEQ. ID. NO.1. The exosome from the engineered macrophage is the exosome from the macrophage with high expression of PD1; the lipid nucleic acid medicine is prepared by loading GSDMD-N mRNA (messenger Ribonucleic Acid) shown on the basis of SEQ.ID.NO.2 on a cationic liposome. The engineered bionic nucleic acid nano-vesicle is used for preparing an oral squamous cell carcinoma diagnostic kit and a therapeutic drug.

The invention provides application of a P8 gene, or a P8 gene coding protein, or a recombinant vector or host bacteria containing a P8 gene coding region in improvement of GFP (Green Fluorescent Protein) expression quantity and / or inhibition of degradation of an mRNA (Messenger Ribonucleic Acid) attenuated substrate taking GFP as a reporter gene. The research finds that the P8 has a silence inhibition function, can inhibit degradation of a nonsense mediated mRNA decay substrate taking GFP as a reporter gene and degradation of an endogenous nonsense mediated mRNA decay (NMD) substrate of arabidopsis thaliana, can improve the mRNA expression quantity of AT1G0106020, RPS6, SMG7, AT5G35490, AT5G64430, AT1G36730, AT4G3900 and AT5G22570, and can reduce the expression quantity of AT1G72450 and AT2G400, and the research result lays a foundation for clarification of the function of the P8.

The invention develops a method and a model for predicting mRNA (messenger ribonucleic acid) translated protein products based on deep learning. Specifically, the invention designs a method for accurately predicting a transcriptome horizontal translation product based on a deep learning method, and the method is used for predicting a translation site and a translation product of a transcript sequence to form a TRANSAID model. The TRANSAID model adopts a unique sequence coding strategy and a deep learning architecture, local sequence features and a long-distance dependency relationship can be captured at the same time, and the prediction accuracy is greatly improved; transcript sequences of different species can be predicted, and cross-species prediction ability appearing for the first time in the field is achieved; and different influences of 5 'UTR and 3' UTR regions on translation regulation and control can be identified.

The invention provides a varicella-zoster virus mRNA (messenger Ribonucleic Acid) vaccine and application thereof. The invention firstly provides an mRNA molecule, a coding region sequence of the mRNA molecule comprises a nucleotide sequence for coding an amino acid sequence as shown in SEQ ID NO: 1, and the coding region sequence preferably comprises a nucleotide sequence as shown in any one of SEQ ID NO: 2 to SEQ ID NO: 11, or a nucleotide sequence which has at least 93% similarity with the nucleotide sequence as shown in any one of SEQ ID NO: 2 to SEQ ID NO: 11 and codes the same amino acid sequence. When the mRNA molecule is used for preparing the vaccine, the production cost of the vaccine can be reduced, the physicochemical property of the vaccine is stable, the protein expression is improved to enhance the immune effect of the vaccine, and the humoral immunity and cellular immunity effects of the VZV-gE specificity are enhanced.

The invention discloses an echinococcosis mRNA (messenger Ribonucleic Acid) vaccine as well as a preparation method and application thereof. The preparation method of the mRNA vaccine for the echinococcosis comprises the following steps: carrying out codon optimization on a modified target antigen protein, then assembling the modified target antigen protein with 5 'UTR, 3' UTR and Poly (A) tail, carrying out gene synthesis, then cloning the synthesized gene into a pUC57 plasmid, and sequentially carrying out plasmid linearization, in-vitro transcription and purification on the constructed recombinant plasmid to prepare an mRNA molecule, thereby obtaining the mRNA vaccine for the echinococcosis. Finally, mRNA molecules are wrapped in lipid nanoparticles through a microfluidic method to form the mRNA vaccine for the echinococcosis, and immune effect evaluation is carried out on the mRNA vaccine for the echinococcosis. Experiments prove that the prepared mRNA vaccine for the echinococcosis can activate humoral immunity and cellular immunity of mice at the same time, can provide an effective protection effect for the mice attacking insects, and has a wide application prospect in the aspect of preventing and / or treating the echinococcosis.

The invention relates to a preparation method of a binary guanidyl block copolymer (Poly-PEG-GUA) for nucleic acid transfection of human vascular endothelial cells (HUVEC). According to the invention, N-(2-(3-carbamyl guanidyl) ethyl) methacrylamide with different proportions is subjected to reversible addition-fragmentation chain transfer (RAFT) polymerization to polyethylene glycol modified 4-cyano-4-(phenyl thioformyl sulfenyl) valeric acid (PEG-CPADN), so that five kinds of binary guanidyl block copolymers with different molecular weights are constructed; the HUVEC gene and messenger ribonucleotide (EGFP-mRNA) of green fluorescent protein are assembled in the HUVEC for screening of transfection efficiency, and the optimal molecular weight for HUVEC transfection is optimized. Experimental results show that the Poly-PEG-GUA with the molecular weight of 53575 Daltons can be used for effectively delivering green fluorescent protein (EGFP) mRNA (messenger ribonucleic acid) to HUVEC (human umbilical vein endothelial cells), and the highest transfection efficiency is shown. The optimized Poly-PEG-GUA in the invention has a certain reference value for the research and development of subsequent cardiovascular transfection products.

The invention belongs to the technical field of tumor vaccines, and particularly relates to an mRNA (messenger Ribonucleic Acid) vaccine for coding tumor antigen epitopes as well as a preparation method and application thereof. In order to overcome the defect of immune escape caused by insufficiency or loss of a single antigen, the invention provides an mRNA vaccine capable of simultaneously coding a plurality of tumor antigen epitopes, and the tumor antigen epitopes are selected from high-frequency mutation epitopes of human tumor driving genes, such as G12D, G12V and G12C mutations of RAS genes; the antigenic epitopes can be used for preparing antigenic epitopes related to common viruses of human tumors, such as HPV16E6 / E7, EBV LAMP1 or CMV pp65, and tumor high-expression carcino-embryonic antigen gene epitopes, such as MAGE-A4, NY-ESO-1, WT1, and the like. The mRNA vaccine is obtained by serially expressing a plurality of tumor antigen epitopes and encapsulating and delivering lipid nanoparticles. Experiments prove that the compound can effectively prevent and treat various tumors and has a wide application prospect.

A composition for genetic editing of a hydroxyacid oxidase 1 (HAO1) gene, comprising: (a) a messenger RNA (mRNA) encoding a Cas12i2 polypeptide, (b) a guide RNA (gRNA) targeting the HAO1 gene; and (c) lipid excipients, which optionally form lipid nanoparticles. Also provided herein are methods for genetic modification of the HAO1 gene in host cells with the composition provided herein.

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 belongs to the field of biological materials, and particularly relates to a multifunctional DNA nanometer material, a preparation method and application of the multifunctional DNA nanometer material in treatment of traumatic brain injury secondary encephaledema. The multifunctional DNA nano material comprises a plurality of deoxyribozyme (DNAzyme) targeting C1q mRNA (messenger Ribonucleic Acid) and a repeating unit which is integrally connected with G-quadruplex / Hemin in series, wherein the G-quadruplex / Hemin is labeled by streptavidin SA and biotin and is used for scavenging free radicals. The DNAzyme for silencing the C1q gene of the mouse is designed on the basis of a bioinformatics method, and the C1q gene overexpressed in an inflammation model can be knocked down to an approximate normal level. The RCA technology mediated self-assembled nano material SA-B / H has excellent enzyme mimetic activity, can effectively remove free radicals such as H2O2 and O2 <.->, and has the potential of in-vivo oxidation resistance. In-vitro experiments prove that SA-B / H can effectively relieve high-level oxidative stress of cells caused by H2O2 stimulation.

The present disclosure provides siRNAs, modifiers, conjugates and uses thereof for targeted regulation of Factor 11 of coagulation (FXI) gene expression. A series of siRNAs are designed based on an FXI messenger ribonucleic acid (mRNA) sequence, alternate modification is carried out, and modification is carried out by utilizing a group of specific modification templates. Cellular and animal experiment results show that some alternately modified and specific template modified oligonucleotide sequences can significantly inhibit the expression of the FXI gene, and can be used for developing anticoagulant drugs.

The invention discloses a diselenide-bond-containing poly-beta amino ester carrier for mRNA delivery and a preparation method and application thereof, and the preparation method of the diselenide-bond-containing poly-beta amino ester carrier comprises the following steps: taking a synthesized diselene-1, 6-hexanediol diacrylate monomer (DSEDA) and hydrophobic amine as raw materials to react to obtain a product as a polymer intermediate; the raw material of the hydrophobic amine is one of C8, C12 and C16; the # imgabs0 # hydrophilic amine raw material is one of 2A1, 2A4 and 2A5; a diselenide bond is introduced into a main chain of the structure of the synthesized linear cationic polymer product, tertiary amine N capable of being protonated into cations exists in the main chain structure, and the tertiary amine N can be effectively combined with nucleic acid with negative charges through electrostatic interaction, so that the nucleic acid loading rate is increased; according to the invention, hydrophobic alkane chains with proper number and length are provided, a hydrophobic cavity can be formed when the nanoparticles are formed, the stability of the nanoparticles is improved, and the nanoparticles have good application in delivery of mRNA (messenger Ribonucleic Acid) molecules.

The present disclosure provides a modified oligonucleotide sequence and its application. A series of siRNAs are designed based on the angiotensinogen (AGT) messenger ribonucleic acid (mRNA) sequence, and are alternately modified and modified using a specific set of modification templates. The results of cell and animal experiments show that some alternately modified and specifically template-modified oligonucleotide sequences can significantly inhibit the expression of the AGT gene, and can be used for developing drugs for treating related diseases such as hypertension.

The invention discloses a polyethylene glycol complexing agent as well as a preparation method and application thereof and belongs to the technical field of medicines. The polyethylene glycol complexing agent comprises the following components in percentage by mass: 1-2% of mesenchymal stem cell source exosome modified by miRNA-138-5p, 1-2% of mesenchymal stem cell source exosome modified by miRNA-21, 1-2% of mesenchymal stem cell source exosome modified by lncGm36569, 1-2% of mesenchymal stem cell source exosome modified by mRNA of SNARE family protein, 1-2% of mesenchymal stem cell source exosome modified by mRNA of SNARE family protein and the balance of water. 1-2% of mesenchymal stem cell source exosome modified by mRNA (messenger Ribonucleic Acid) of syntachilin, and the balance of polyethylene glycol. The polyethylene glycol complexing agent disclosed by the invention can reconstruct spinal cord continuity and improve a spinal cord injury microenvironment, so that a neurological function is recovered.

The invention relates to an mRNA (messenger Ribonucleic Acid) vaccine targeting FomA and application of the mRNA vaccine in immunotherapy of esophageal squamous carcinoma in the technical field of tumor immunotherapy. The problems that in the prior art, a specific targeting vaccine for the fusobacterium nucleatum membrane protein FomA lacks, traditional antibiotics can only kill extracellular bacteria and cannot remove intracellular colonized fusobacterium nucleatum, and cellular immunity cannot be effectively activated to remove fusobacterium nucleatum colonized in tumor tissue; the immunotherapy drug resistance of esophageal squamous carcinoma caused by fusobacterium nucleatum infection is difficult to reverse. According to the technical scheme, an mRNA molecule with a fusobacterium nucleatum FomA extracellular domain tandem repeat sequence and a lipid nanoparticle delivery system are coded, an extramembrane segment tandem repeat immune enhancement technology is adopted for design, two extracellular ring sequences are repeated for 2-5 times and connected through a connector sequence, lipid nanoparticles are composed of optimized quaternary lipids, and the lipid nanoparticles are prepared from the quaternary lipids. And a PD-1 monoclonal antibody is combined to activate FomA specific CD8 + T cell immunoreaction, so that comprehensive removal of intracellular and extracellular bacteria and bacteria targeted immune remodeling are realized.

The invention discloses an mRNA (messenger Ribonucleic Acid) vaccine of varicella-zoster virus as well as a preparation method and application of the mRNA vaccine. According to the mRNA vaccine provided by the invention, a gE antigen sequence is subjected to codon optimization; then selecting a proper promoter, 5 'UTR, 3' UTR and 3 '-terminal PolyA to combine into complete mRNA nucleic acid for coding the varicella-zoster virus, screening to obtain two groups of mRNA nucleic acid for coding the varicella-zoster virus with both expression level and stability, and adopting a novel cationic lipid imidazopyridyl lipid compound to prepare a vaccine liposome. The targeting property in drainage of lymph nodes is improved, and the humoral immunity and cellular immunity levels excited by the vaccine in animal bodies are remarkably improved.

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 provides an anti-inflammatory substance and application thereof, and relates to the technical field of molecular biology. The docosahexaenoic acid can be used for effectively inhibiting expression of mRNA (messenger ribonucleic acid), protein and supernatant of IL-1beta (interleukin-1beta) of RAW264.7 cells induced by LPS (lipopolysaccharide); in addition, the docosahexaenoic acid can play a role in relieving inflammation in a transdermal administration mode, and the technical effect of inhibiting or treating inflammation in a non-invasive and safe mode is achieved.

The invention discloses an mRNA (messenger ribonucleic acid) vaccine for preventing and / or treating pseudorabies and application of the mRNA vaccine. Codon optimization is performed on a gene sequence of a pseudorabies virus gD protein antigen to obtain an optimized gene sequence of the pseudorabies virus gD protein antigen; the pseudorabies virus truncated gD protein antigen is obtained by optimizing the sequence of the pseudorabies virus gD protein antigen, the gene sequence of the truncated gD protein antigen is subjected to codon optimization, and experiments show that the optimized pseudorabies virus truncated gD protein antigen has higher expression quantity; the sequence-optimized pseudorabies virus truncated gD protein is further prepared into an mRNA vaccine, and after the mRNA vaccine is used for immunizing mice and piglets, it is found that the mRNA vaccine of the sgD protein can play an immune protection role on the mice and the piglets, and the mRNA vaccine is obviously superior to commercially available pseudorabies inactivated vaccines.

The invention discloses a recombinant PB transposase mRNA (messenger ribonucleic acid) and PiggyBac vector system and application of the recombinant PB transposase mRNA and PiggyBac vector system. The invention provides a recombinant PB transposase mRNA (messenger ribonucleic acid), the nucleotide sequence of the recombinant PB transposase mRNA is shown as SEQ ID NO: 11, and the 5'end of the recombinant PB transposase mRNA contains a cap structure. The invention provides an mRNA type recombinant PB transposase: PBase-Cap-mRNA, so that the risk that a PB transposase plasmid is inserted into a host cell genome is avoided, and the efficiency of inserting a donor plasmid into the host cell genome is improved. The recombinant PB transposase mRNA is capped, so that the stability of the mRNA is improved, the translation of the mRNA is promoted, and the transposon efficiency is improved. The CHO cells are co-transfected by recombining PB transposase mRNA and donor plasmids, so that the efficiency of transfecting host cells by the donor plasmids is improved, and the construction period of stable cell strains is remarkably shortened.

The invention provides antisense oligonucleotide of IL-17A mRNA (messenger Ribonucleic Acid) as well as application and a medicinal composition of the antisense oligonucleotide, and relates to the technical field of biological medicines. The nucleotide sequence of the antisense oligonucleotide of the IL-17A mRNA provided by the invention is as shown in SEQ ID NO.1, 3, 5 to 18, 20 to 23, 26 to 28 or 31. The antisense oligonucleotide can be specifically combined with IL-17A mRNA, RNase H is recruited after the antisense oligonucleotide is combined with the IL-17A mRNA, then degradation of the IL-17A mRNA is achieved, synthesis of IL-17A protein is prevented, and the antisense oligonucleotide can be used for preparing drugs for treating IL-17A related diseases.

Provided herein are engineered flavivirus heterotetrameric proteins (.e.g., Envelope and / or Membrane proteins) comprising at least one stabilizing amino acid substitution. The engineered flavivirus proteins form a stabilized heterotetramer structure. Messenger ribonucleic acid vaccines encoding the engineered flavivirus proteins are also provided. The disclosure also provides methods of eliciting an immune response and / or neutralizing antibodies to flavivirus in a subject.

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.