172 results about "Messenger ribonucleic acid" patented technology

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 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 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 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 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 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 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.

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.

The invention discloses a method for efficiently producing general type CAR-T. The general type CAR-T. Specifically, the invention provides a method for efficiently producing universal CAR-T. The method comprises the following steps: (s1) providing a T cell to be edited, and carrying out activated culture on the T cell to obtain an activated T cell; (s2) gene introduction: transfecting the activated T cell by using the LVV integrated with the CAR gene so as to obtain the T cell of which the genome is integrated with the CAR gene; (s3) gene knockout: transfecting the T cell obtained in (s2) by using LNP (Leukocyte Natriuretic Peptide) coated with Cas9mRNA (Cas9 Messenger Ribonucleic Acid) and sgRNA (Single Guide Ribonucleic Acid) so as to obtain a T cell in which the TCR gene and the CD7 gene are knocked out; and (s4) culturing the T cells obtained in the step (s3) so as to obtain the universal CAR-T. According to the method, the UCAR-T production cost can be remarkably reduced, the preparation period is shortened, and commercialization of shelf-type cell therapy is promoted.

The invention discloses a saccharomyces cerevisiae microbiome RNA (Ribonucleic Acid) sequencing data analysis method based on long read length sequencing, which is characterized in that the structure of a gene is updated and optimized by efficiently comparing reference genome data and identifying a new transcript and a new gene transcript of a known gene, so that complete data is provided for analyzing a yeast mRNA (Messenger Ribonucleic Acid) and ncRNA (Non-coding Ribonucleic Acid) structure; and the analysis accuracy and effectiveness are improved.

The present disclosure provides a modified oligonucleotide sequence and use thereof. A series of siRNAs were designed based on the angiotensinogen (AGT) messenger ribonucleic acid (mRNA) sequence, which were alternately modified or modified using a specific set of modification templates. The results from cell and animal experiments demonstrated that some oligonucleotide sequences with alternating modifications and specific template modifications can significantly inhibit AGT gene expression and may be used for the development of medicaments for treating hypertension and other related diseases.

This application relates to modified H5 influenza hemagglutinin polypeptides and messenger ribonucleic acids (mRNAs) encoding the same, as well as compositions and vaccines comprising the same and methods of using the same, such as in the prevention and / or treatment of diseases or conditions caused by influenza A viruses, particularly influenza A virus, subtype H5, such as H5N8 or H5N1.

The invention discloses a human papilloma virus mRNA (messenger ribonucleic acid) detection kit for auxiliary diagnosis of cervical cancer patients. The human papilloma virus mRNA detection kit comprises a nucleic acid probe group and a series of nucleic acid probes AMP1-AMP5, wherein the nucleic acid probe group is used for being combined with a human papilloma virus mRNA target, and the nucleic acid probes AMP1-AMP5 are used for signal amplification. The human papilloma virus mRNA detection kit provided by the invention can assist pathologists in identifying and diagnosing cervical cancer patients, and provides a basis for clinicians to formulate a therapeutic schedule.

The invention belongs to the technical field of forensic medicine, and particularly relates to an mRNA marker combination, a product and application thereof and a forensic human menstrual blood or human menstrual blood spot detection method. The mRNA marker combination comprises a reference gene, a human blood specific mRNA marker and a human menstrual blood specific mRNA marker; the human blood specific mRNA marker is composed of HBA, HBB, ALAS2 and GYPA; the human menstrual blood specific mRNA marker is composed of MMP7, MMP10, SFRP4 and STC1. Standardized identification suggestions are given according to mRNA marker combination expression conditions, the problems of insufficient specificity, flow disorder and the like in the prior art are solved, human menstrual blood or human menstrual blood spots can be accurately distinguished from peripheral blood and other body fluids, cross-platform compatible standardized detection is realized, evidence support is provided for missing cases, and the detection method is suitable for clinical application. The method has important practical significance for improving the forensic physical evidence identification efficiency.

The invention discloses a construction method of a glomerular IgA deposition mouse model, and relates to the technical field of animal model development and glomerular IgA dyeing. Comprising the following steps: obtaining Cas9 mRNA (messenger ribonucleic acid), guideRNA (ribonucleic acid) and donor DNA (deoxyribonucleic acid) in an in-vitro transcription manner; the method comprises the following steps: carrying out microinjection on Cas9 mRNA (messenger ribonucleic acid), gRNA (guide ribonucleic acid) and donor DNA (deoxyribonucleic acid) into fertilized eggs of a C57BL / 6J mouse; carrying out genotype identification on the F0 generation of birth mice through PCR (Polymerase Chain Reaction) amplification and sequencing; mating the F0-generation positive mouse with a wild type C57BL / 6J mouse, and breeding to obtain an F1-generation mouse; and spontaneous glomerular IgA deposition appears in 24 weeks after the F1 generation heterozygote mouse is born. According to the method, accurate mutation is introduced by utilizing a homologous recombination repair mechanism to construct a glomerular IgA deposition model, the efficiency is high, and the off-target risk is low.

The invention relates to hypoxia response therapeutic VEGFA (vascular endothelial growth factor A) mRNA (messenger Ribonucleic Acid) and application thereof. The mRNA comprises a 5'end cap, a 5 'UTR (Untranslated Region) containing a Kozak sequence, VEGFA ORF (Open Region Fragment), a 3' UTR containing an RNA (Ribonucleic Acid) binding protein HuR binding site, a RhoBAST fluorescent aptamer at the tail end of the 3 'UTR and a PolyA tail. According to the design, through a HuR hypoxia-dependent nuclear plasma transport mechanism, the stability of mRNA in hypoxic cells is improved by 2.5 times, the protein expression quantity is improved by 2 times, and proliferation of endothelial cells is remarkably promoted. Further disclosed is a VEGFA mRNA delivery system based on engineered extracellular vesicles (EVs): EVs surface modified kidney targeting peptide LTH. The system is efficiently accumulated in ischemic kidneys, VEGFA expression is remarkably enhanced, and abnormal vascular hyperplasia of external renal organs is avoided. Animal experiments prove that the survival rate of a renal ischemia-reperfusion injury model can be increased to 100% by intravenous injection of drug-loaded EVs, and the capillary density is remarkably increased 7 days after treatment. The invention is suitable for treating ischemic diseases, organ ischemia reperfusion injury or chronic wounds and the like, and has the advantages of accurate targeting, hypoxia response, high stability and safety.

Provided herein are RNA molecules (e.g. self-amplifying messenger ribonucleic acids (samRNA)) comprising modified nucleotides, such as N1-methyl-pseudouridine.

The invention discloses an application of an engineered mRNA (messenger Ribonucleic Acid) medicine for coding COL3A1 protein in resisting skin photoaging. According to the method, accurate rational design and optimization are carried out on the 5'untranslated region (UTR) of the hCOL3A1 mRNA, so that the translation efficiency and the protein yield of the hCOL3A1 mRNA are greatly improved, the expression level of the hCOL3A1 target protein far beyond the conventional sequence in vivo and in vitro is realized, and the type III collagen is efficiently and endogenously synthesized in skin cells. Experimental results show that the engineered mRNA can effectively reduce the skin oxidative stress level, inhibit cell aging and promote endogenous synthesis and deposition of corium layer collagen, so that the barrier function of photoaged skin is remarkably improved, the dermis thickness is increased, the tissue structure is repaired, and systemic toxicity or immune side effects are not observed. The invention provides a novel strategy with high efficiency and safety for resisting skin photoaging.

The invention discloses a teneplase mRNA (messenger Ribonucleic Acid) medicine and application thereof. The active ingredient of the medicine provided by the invention is mRNA (messenger ribonucleic acid) as shown in SEQ ID NO.5. The invention also protects a recombinant plasmid of the teneplase as shown in SEQ ID NO. 4. Specific DNA molecules are obtained through a series of design and sequence optimization, specific recombinant plasmids are synthesized through gene synthesis, the specific recombinant plasmids are subjected to in-vitro transcription, cell supernatant protein is obtained through transfection of mRNA of different amounts at different time points after transfection, and the cell supernatant protein is used for preparing the recombinant protein. According to the present invention, it is detected through ELISA that the tinipase mRNA can be effectively expressed in different cells of different species, such that the pioneering significance is provided for the development of the tinipase mRNA drug.

The invention relates to an mRNA (messenger Ribonucleic Acid) vaccine aiming at a fever with thrombocytopenia syndrome virus (SFTSV) and application of the mRNA vaccine. According to the vaccine, Gn and Gc glycoproteins are co-expressed in vivo, and four optimized mutations are introduced at key sites: N33Q, N63Q and K288R of the Gn protein and S962A of the Gc protein. The mutation can remove glycosylation, enhance protein conformational stability and reduce Gc-mediated membrane fusion activity, thereby improving the immunogenicity and safety of the antigen. The mRNA vaccine provided by the invention can induce a neutralizing antibody with a higher level; in a mouse challenge experiment, the vaccine shows higher survival rate and lower virus load, and has an excellent protection effect. Therefore, the mRNA vaccine disclosed by the invention has a wide application prospect in the aspect of preventing the severe fever with thrombocytopenia syndrome virus.

The invention discloses antibody coupled lipid nanoparticles for targeted heart delivery of mRNA (messenger Ribonucleic Acid) as well as a preparation method and application of the antibody coupled lipid nanoparticles, and belongs to the field of biological medicine pharmacy. The antibody-coupled lipid nanoparticles are obtained by inserting phospholipid coupled with a Myh7 antibody into lipid nanoparticles wrapping mRNA (messenger ribonucleic acid); the mass ratio of the phospholipid coupled with the Myh7 antibody to the lipid nanoparticles wrapping the mRNA is (5-10): 1. According to the present invention, the Myh7 antibody is coupled with the lipid nanoparticles, such that the delivery efficiency of the lipid nanoparticles to the heart is substantially enhanced, the delivery efficiency at the myocardial injury position is particularly efficient, the mRNA activity is retained, and the efficient approach is provided for the preparation of the mRNA drug by using the lipid nanoparticles or the treatment of the heart-related diseases by using the vaccine therapy.

The invention relates to a functionalized magnetic bead which is a magnetic bead formed by wrapping a magnetic bead with bifunctional nucleic acid and can be specifically combined with mRNA (messenger ribonucleic acid). The fungal mRNA extraction kit composed of the functionalized magnetic beads comprises a grinding material, a lysis solution I, a lysis solution II, a magnetic bead combination solution, a cleaning solution I, a cleaning solution II and an eluent. The mRNA extraction method comprises the following steps: sequentially adding the grinding material, the lysis solution I, the lysis solution II, the magnetic bead binding solution, the cleaning solution I, the cleaning solution II and the eluent after sample pretreatment to obtain an mRNA product. The traditional mRNA extraction method is broken through, high-quality mRNA is obtained, and the method has the advantages of simplicity in operation, safety, no toxicity, high sensitivity, good repeatability and low cost. The obtained mRNA can provide a high-quality template for RT-PCR (Reverse Transcription-Polymerase Chain Reaction) detection, the detection specificity and sensitivity are improved, and the mRNA has a wide application prospect in the fields of clinical diagnosis of diseases, judicial expertise, food safety detection, microbiological detection, molecular biology and the like.

The invention discloses an efficient blood brain barrier crossing adeno-associated virus mutant and application, and relates to the technical field of biological medicine. A587Q588 in the amino acid of the AAV9 serotype capsid protein is replaced by a heterologous peptide; the heterologous peptide is a polypeptide consisting of any one of amino acid sequences in DGTIQAPFR (Databine Glycine Triphosphate Quantitative Amplified Polypeptide Receptor) or DGTTFTPPR ( The infection efficiency, mRNA (messenger ribonucleic acid) and protein expression of the SG302 and the SG303 on brain, spinal cord and thalamic neurons of a mouse are obviously higher than those of AAV9, and the infection capacity on the liver is obviously lower than that of the AAV9. The SG302 and the SG303 are serotype mutants with good specificity for a nervous system, the high infection efficiency can reduce the administration dosage, and the low hepatotrophy characteristic can improve the safety performance.