269 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 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 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 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 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 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 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 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 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.

The invention discloses a porcine reproductive and respiratory syndrome virus mRNA (messenger Ribonucleic Acid) molecule and application thereof, and four mRNA vaccines GP35m-LNP, GP45m-LNP, GP345m-LNP and GP2345m-LNP are designed by combining structural protein GP2a, GP3, GP4 and GP5 genes of a PRRSV FJ1402 strain of NADC30-like. Mouse test results show that the GP345m-LNP can simultaneously induce strong humoral and cellular immune response, the GP2345m-LNP is secondary, and the effect is superior to that of an inactivated vaccine (only inducing humoral immunity). After immunization, the PRRSV FJ1402 strain is adopted for counteracting toxic substances, the virus load in blood and lungs of a GP345m-LNP group is obviously reduced, pathological injuries of the lungs are obviously relieved, the immune effect is superior to that of an inactivated vaccine group, and the vaccine has a relatively good application prospect.

The invention provides a lipid nanoparticle for the targeted combined delivery of a CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-Cas9) system and a single-stranded DNA (deoxyribonucleic acid) repair template of the liver, and the lipid nanoparticle is prepared from an ionizable lipid ALC-0315, a PC (polycarbonate) lipid DOPC (dioctyl-phthalate), cholesterol and DMG-PEG (dimethyl glycol-polyethylene glycol) (2000) according to a molar ratio of 50: 10: 38.5: 1.5. The lipid nanoparticles can simultaneously package Cas9 mRNA (messenger ribonucleic acid), sgRNA (small guide ribonucleic acid) and a single-stranded DNA (deoxyribonucleic acid) repair template required by homologous directional repair (HDR) gene editing according to a certain proportion to prepare All-in-one LNP. According to the All-in-one LNP, the three nucleic acids are successfully delivered in a liver-targeted combined manner, HDR editing is successfully performed on the liver of a young rat, and an accurate and efficient tool is provided for in-vivo editing.

The invention belongs to the field of biological medicine, and particularly relates to an artificially synthesized polypeptide P2 and application thereof in resisting herpes virus infection. According to the invention, a polypeptide P2 of key amino acid residues (77N, 80I, 82N, 84N, 85N and 129F) combined with virus glycoprotein gD in a specific targeting host cell surface receptor Nectin-1 is designed and obtained through an RFdiffusion algorithm; the polypeptide P2 can significantly inhibit PRV infection, and has no significant cytotoxicity; the polypeptide P2 can be used for remarkably down-regulating PRV UL42 protein expression and gB mRNA (messenger Ribonucleic Acid) level; based on the conservative property of Nectin-1 in a herpes virus invasion mechanism, the polypeptide P2 can also be used for inhibiting infection of other herpes viruses (such as HSV-1 and HSV-2), and an important strategy is provided for developing novel anti-herpes virus drugs.

The invention discloses an application of an mRNA combination in predicting the curative effect of myocardial peptide in treating myocardial ischemia-reperfusion injury, and belongs to the technical field of biology. The mRNA combination comprises Asb10 (Asb10) and Egr2 (Egr2); the nucleotide sequence of the Asb10 is as shown in SEQ ID NO. 1, and the nucleotide sequence of the Egr2 is as shown in SEQ ID NO. 2. Experiments prove that compared with a normal mouse, the expression of Asb10 in a model group is remarkably reduced, the expression of Egr2 is remarkably improved, and compared with the model group and a cardiomyopeptide group, the level of Asb10 is remarkably improved, and the level of Egr2 is remarkably reduced. The ROC curves of Asb10 and Egr2 after myocardial peptide treatment are constructed, and the AUC of Asb10 and Egr2 is 0.816 and 0.762 respectively. The invention provides a more effective monitoring means and a new thought for more stably predicting the curative effect of myocardial peptide on myocardial ischemia-reperfusion injury at low cost.

The invention provides an mRNA (messenger Ribonucleic Acid) molecule aiming at varicella-zoster virus, an mRNA vaccine containing the molecule and application of the mRNA vaccine. The mRNA molecule disclosed by the invention is optimized aiming at glycoprotein E (VZV gE protein) of varicella-zoster virus, and the optimized mRNA molecule can play a role in effective immunization and is high in safety.

The present invention pertains to the technical field of biomedicine, and specifically relates to a gene delivery system and use thereof in the preparation of a tumor therapeutic drug. The present invention relates to a technical means for inducing differentiation of tumor cells into mature cells, which utilizes messenger ribonucleic acid to regulate the expression of HNF4α in tumor cells, inhibits the malignant phenotype of malignant solid tumor cells, and achieves the effect of treating malignant solid tumors, thereby being applied to a preparation method and use of a solid tumor drug.

An mRNA molecule is disclosed. The mRNA molecule contains a polynucleotide encoding an M1R antigen of Mpox and a polynucleotide encoding an RBD antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and further contains a polynucleotide encoding an A35R antigen of Mpox. An application of the mRNA molecule in the preparation of an mRNA vaccine against Mpox or SARS-CoV-2 is further disclosed. Compared to an mRNA vaccine encoding separately corresponding antigens, the provided mRNA vaccine encoding a fusion antigen can induce considerable or even higher-level neutralizing antibody responses against Mpox and SARS-CoV-2, and provides 100% immune protection against the lethal challenge of ectromelia virus. The vaccine is obtained by synthesizing a single mRNA molecule and encapsulating the single mRNA within lipid nanoparticles. Therefore, the single-component fusion mRNA vaccine has a wider application prospect than multivalent mRNA vaccine compositions.

Aspects of the disclosure relate to mRNAs comprising a relatively low abundance of cytidine: adenosine (CA) dinucleotides that benefit from increased stability relative to mRNAs containing more CpA dinucleotides. The disclosure also relates to methods of modifying an mRNA sequence to improve stability. In some aspects, the disclosure relates to mRNAs comprising modified mRNA sequences with relatively reduced numbers of CpA dinucleotides, and compositions comprising mRNAs with relatively reduced numbers of CpA dinucleotides.

The invention provides application of IGF2BP3 serving as a target spot in preparation of a medicine for treating fused genotype leukemia, and particularly relates to application of IGF2BP3 serving as a target spot in preparation of a medicine for treating mRNA (messenger ribonucleic acid) high-stability fused genotype leukemia. The mRNA high-stability fusion gene comprises but is not limited to fusion genes such as PAX5-ETV6, STK38-PXT1 and the like. The medicine comprises an IGF2BP3 gene specific interfering RNA (Ribonucleic Acid) and an IGF2BP3 inhibitor, and the IGF2BP3 inhibitor comprises but is not limited to Vitonetog. The invention provides the application of the medicine taking the IGF2BP3 as the target spot in treating mRNA high-stability fused genotype leukemia for the first time; the invention discloses the effect of the IGF2BP3 in the carcinogenic function of the fusion gene, provides a new therapeutic target and an effective drug for the fusion genotype leukemia, and provides possibility for further improving the clinical curative effect of leukemia patients and improving the prognosis and survival of the leukemia patients.

The invention provides an mRNA (messenger Ribonucleic Acid) containing a nucleotide sequence for coding collagen, and a composition containing the mRNA and a delivery carrier. Introduction of the mRNA molecule into a subject by the composition may be used to improve skin conditions.

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 an mRNA vaccine composition for the prevention of enterovirus A71 (EV-A71) infection. The composition comprises an mRNA encoding the VP1 protein of EV-A71 and lipid nanoparticles (LNPs) comprising specific cationic lipids. Compared with the conventional cationic lipid system, the imidazopyridyl cationic lipid A5 with strong membrane fusion capability is adopted, so that obvious neutralizing antibody and cellular immune response can be induced under single-time and low-dose immune conditions, and excellent safety and children applicability are shown.