110 results about "Messenger ribonucleic acid" patented technology

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 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 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 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 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.

The invention discloses a mycobacterium tuberculosis mRNA (messenger Ribonucleic Acid) vaccine as well as a construction method and application thereof, and belongs to the technical field of biological medicines. The technical problem to be solved is to provide a novel mycobacterium tuberculosis mRNA vaccine which is low in dosage, high in safety and lasting in immune memory. According to the technical scheme, the preparation method is characterized by comprising the following steps: carrying out tandem expression on antigens for coding Hsp65 and Mpt83, constructing mRNA molecules by combining tPA signal peptide (SEQ ID NO: 1), an MITD sequence (SEQ ID NO: 5) and flexible Linker (SEQ ID NO: 6-7), and carrying out codon optimization (an mRNA secondary structure and GC content) and a lipid nanoparticle (LNP) encapsulation process to finally obtain the novel mycobacterium tuberculosis mRNA vaccine.

Provided herein are vaccine composition comprising a chemically-modified messenger ribonucleic acid (mRNA) encoding a hMPV fusion (F) glycoprotein and / or a chemically-modified mRNA encoding a hRSV F glycoprotein formulated in a lipid nanoparticle, and related methods for inducing an antigen- specific immune response.

The invention discloses a method for rapidly extracting mRNA from mRNA-LNP, which comprises the following steps: adding a polar organic solvent and a non-polar organic solvent into an mRNA-LNP sample to obtain a mixed solution; standing or centrifuging the mixed solution, and taking an upper-layer solution to obtain an mRNA (messenger Ribonucleic Acid) solution; wherein the polar organic solvent can be selected from at least one of alcohols, ketones and amides; the non-polar organic solvent can be selected from at least one of alkanes, halogenated hydrocarbons and esters. By utilizing the method provided by the invention, the mRNA can be quickly and efficiently extracted from the mRNA-LNP, the operation is simple, and the sample loss is small.

The utility model discloses a micro-fluidic chip for synthesizing mRNA (messenger ribonucleic acid) lipid nanoparticles, which comprises a chip main body, a top template is fixedly arranged at the upper end of the chip main body, and a bottom template is fixedly arranged at the bottom end of the chip main body. A small number of herringbone fishbone mixers are used to form a double-side mixing promotion system, on the premise of ensuring the synthesis quality, the reagent cost is reduced, a better mixing effect is realized, meanwhile, the chip and each structural parameter in the chip are elaborately optimized, the fluid can be accurately regulated and controlled, and the efficiency is improved. The method provided by the utility model is beneficial to synthesis of the bottom layer template mRNA bottom layer template lipid nanoparticles with higher quality, narrower particle size distribution and better wrapping effect, indirectly improves the production benefit, and further embodies the advantages in cost control and resource utilization compared with the prior art.

The invention discloses an mRNA (messenger ribonucleic acid) translation enhancement tool (MiniCURE) and application thereof, and belongs to the technical field of gene editing. The Mini CURE provided by the invention utilizes a natural m6A-YTHDF1 pathway for regulating mRNA stabilization and translation, the off-target effect generally related to a DNA editing tool is avoided, and data confirms that the Mini CURE has an effective effect of increasing protein expression. Transcriptomic and proteomic analysis proves that the minimum off-target activity is achieved, and compared with a control group, only six proteins in the placenta treated by Mini CURE are up-regulated. The high specificity is crucial to clinical translation because maternal or fetal complications may be aggravated by whole body disturbance.

The invention provides a modified oligonucleotide sequence and application thereof. A series of siRNAs are designed based on an angiotensinogen (AGT) 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 AGT genes, and can be used for developing drugs for treating hypertension and other related diseases.

The invention relates to a multi-antigen component PEI lipid delivery system and an anti-avian influenza virus multivalent vaccine comprising the same, belongs to the technical field of biological medicines, and provides a delivery system consisting of PEI, squalene, cholesterol and mPEG. The preparation method comprises the following steps of: constructing mRNA (messenger ribonucleic acid) molecules and a composite vaccine antigen system consisting of prokaryotic expression purified H7N9 avian influenza NP antigen, loading the composite vaccine antigen system into a delivery system to obtain the nanoparticles with a virus-like structure, and displaying the HA protein antigen and the NP antigen in the structure of the nanoparticles in a particle form by the nanoparticles, so that the nanoparticles can be used for preparing the H7N9 avian influenza NP / H7N9 avian influenza NP / H7N9 avian influenza NP / H7N9 avian influenza virus. And the mRNA molecule for coding the NA antigen, which is combined with the mRNA molecule, can be delivered into a cell in a manner of fusing lipid and a cell membrane, so that the mRNA molecule can be effectively expressed to induce a body to generate specific antibody reactions aiming at HA, NA and NP, and the body can also generate specific CTL reactions aiming at HA, NA and NP of different influenza virus strain subtypes.

A gene delivery system and applications thereof in the technical field of biological medicines that is particularly useful in the preparation of drugs for treatment of tumors are disclosed. The gene delivery system and applications relate to technology for inducing the differentiation of malignant tumor cells into mature cells, in which regulating the expression of HNF4 alpha protein in the malignant tumor cells using messenger ribonucleic acid, the malignant phenotype of the malignant solid tumor cells is inhibited, and the effective treatment of the malignant solid tumors is achieved. The gene delivery system and applications are therefore applicable to a method of preparing a drug for treating malignant solid tumors and to a method of treating a patient having a malignant solid tumor.

Described herein are compositions, uses thereof, and methods for treating a viral infection in a host cell or organism infected by the virus, such as coronaviruses, Zika virus, Lassa virus, Crimean Congo hemorrhagic fever virus, hepatitis E virus, and other RNA viruses. Also described herein are synthetic rocaglate compositions, uses thereof, and methods for reducing or inhibiting translation initiation of a messenger ribonucleic acid (mRNA) of a virus in a host cell or organism infected by the virus.

The invention relates to a marker for detecting tumor immune escape and application thereof. The marker comprises at least one of TRIM25 protein, a gene of the TRIM25 protein or mRNA (messenger ribonucleic acid) of the TRIM25 protein. In order to solve the problems existing in existing tumor immune escape detection and treatment, the novel marker TRIM25 is excavated and developed, accurate detection of the tumor immune escape state can be achieved through the novel marker TRIM25, and a more accurate diagnosis basis is provided for clinicians. Meanwhile, related treatment methods and drugs can be developed based on the TRIM25, the pertinence and effectiveness of tumor treatment are improved, the prognosis of tumor patients is improved, and the tumor treatment is promoted to develop towards the precision direction.