5322results about "Active genetic ingredients" patented technology

The invention provides an artificial nucleic acid molecule which is used for improving the expression quantity of target amino acid, polypeptide or protein. The artificial nucleic acid molecule at least comprises a target 5'untranslated region (UTR), a target coding region (CDS) and a target 3 'untranslated region (UTR). Wherein the sequence of the target 5 'UTR is one of the following sequences: 5' UTR of a high-expression gene and a 5 'UTR variant of the high-expression gene. The sequence of the target 3 'UTR is one of the following sequences: 3' UTR of a high-expression gene and a 3 'UTR variant of the high-expression gene. Optionally, the artificial nucleic acid molecule may further comprise, for example, a 5 '-end cap structure (Cap), a PolyA tail. The 5 'UTR and the 3' UTR have regulating effects on translation and stability of nucleic acid molecules, so that the 5 'UTR, the 3' UTR and variants thereof are selected from high-expression genes, the nucleic acid molecules can be further stabilized and are not easy to degrade, and the amount of protein or polypeptide obtained by translation of the nucleic acid molecules can be increased. The invention also provides methods for making, delivering, and using such artificial nucleic acid molecules, as well as the use of the artificial nucleic acid molecules for the treatment and / or prevention of related diseases or disorders.

The invention provides an UTR (Untranslated Region) element H2202 P1-G as well as a construction method and application thereof, and relates to the technical field of mRNA (messenger ribonucleic acid). According to the present invention, the ribosome load prediction and the secondary structure optimization are performed on the natural 5 'UTR of the HIV TAT 202 gene through the BaidleHelix platform, and the obtained HTAT 202 P1 sequence avoids the inhibitory hairpin structure so as to significantly improve the luciferase expression quantity compared to the natural UTR; an ncRNA sequence without a secondary structure is introduced on the basis of the HTAT 202 P1, translation inhibition of a 5 'cap region is further relieved, and the protein expression quantity of the constructed H2202 P1-G mutant (the DNA sequence of the H2202 P1-G is as shown in SEQ NO 1, and the RNA sequence is as shown in SEQ NO 2) is further improved.

The invention provides an UTR element NHP1 as well as a construction method and application thereof, and relates to the technical field of mRNA. A 5 'UTR with a good expression effect is designed by integrating dominant sequences of a human high-expression gene and a pathogen natural UTR, a chimeric structure NHP1 with high ribosome load is predicted through a calculation model, a DNA sequence of the NHP1 is as shown in SEQ NO 1, and an RNA sequence of the NHP1 is as shown in SEQ NO 2; an EGFP report system is adopted on the DNA level to rapidly screen UTR; the translation efficiency is quantitatively evaluated on the RNA level through luciferase mRNA (N1-methyl pseudouridine modification); and the particle size is controlled by a microfluidic technology, so that the optimized UTR-mRNA is efficiently expressed after being delivered.

The invention provides a UTR (Untranslated Region) sequence for improving mRNA (Messenger Ribonucleic Acid) stability and translation efficiency and application of the UTR sequence, and particularly provides an mRNA molecule which comprises a coding region for coding polypeptide or protein and a fragment thereof, a 5 'UTR sequence positioned at the upstream of the coding region and / or a 3' UTR sequence positioned at the downstream of the coding region, the 5 'UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 1, and the 3' UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 2; and / or, the 5 'UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 3, and the 3' UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 4. According to the present invention, the mRNA stability and the translation efficiency are improved through the new and optimized UTR sequence, and the UTR sequence can be used as the element for enhancing the RNA expression efficiency in the nucleic acid treatment drug or the mRNA vaccine so as to provide more and better choices for the mRNA therapy.

Disclosed herein are molecules and pharmaceutical compositions that induce an insertion, deletion, duplication, or alteration in an incorrectly spliced mRNA transcript to induce exon skipping or exon inclusion. Also described herein include methods for treating a disease or disorder that comprises a molecule or a pharmaceutical composition that induces an insertion, deletion, duplication, or alteration in an incorrectly spliced mRNA transcript to induce exon skipping or exon inclusion.

The invention relates to application of an MYZAP overexpression vector in preparation of a medicine for preventing and treating MIRI, and belongs to the technical field of biological medicine. In order to solve the problem that application of gene drugs in prevention and treatment of myocardial ischemia reperfusion injury is limited, the invention provides application of an MYZAP gene overexpression recombinant vector in preparation of drugs for prevention and treatment of myocardial ischemia reperfusion injury, and the MYZAP gene overexpression recombinant vector is an adeno-associated virus vector AAV9-MYZAP for overexpressing MYZAP. Experiments prove that MYZAP overexpression can improve the cardiac function after myocardial ischemia reperfusion, reduce the occurrence rate of arrhythmia and improve the functions of sodium ion channels, potassium ion channels and calcium ion channels of myocardial cells. On the basis, the invention further provides a medicine for preventing and treating myocardial ischemia reperfusion injury, a new strategy is provided for gene therapy of myocardial ischemia reperfusion injury, and the medicine has a wide clinical application prospect.

The invention provides a hypoglycemic peptide which is prepared by taking bovine whey protein as a raw material and is stable in gastrointestinal digestion and absorption. In an in-vitro cell experiment, the peptide fragment can improve the uptake of insulin-resistant HepG2 hepatocytes and synthesize glycogen by using glucose, can promote intestinal endocrine cells NCI-H716 to secrete GLP-1, has a certain synergistic effect, and can further play the effects of promoting GLP-1 secretion and activating a GLP-1 receptor through combined use. An insulin resistance mouse model is constructed by utilizing high-fat diet, and the peptide fragment is adopted for intervention, so that the hypoglycemic peptide is further proved to have obvious effects on losing weight, reducing lipid accumulation and assisting in reducing blood fat, and meanwhile, the hypoglycemic peptide can be used for improving insulin resistance related symptoms. The milk peptide provided by the invention has gastrointestinal digestion stability and hypoglycemic activity, can be used as a functional milk base material for developing food, medicines or health care products with the effect of regulating blood sugar, and is wide in application prospect.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a macrophage Angulin-1 gene and / or an Angulin-1 protein in preparation of medicines and diagnostic products for preventing and / or treating atherosclerosis and related diseases. Research finds that plaque and necrotic core areas of an atherosclerosis animal model are remarkably increased due to macrophage Angulin-1 gene knockout, and disease development is promoted; and the recovery of the expression level of Angulin-1 significantly inhibits the development of lesion. Cell experiments show that Angulin-1 reduces intake of oxidized low-density lipoprotein by down-regulating expression of macrophage LOX-1, so that formation of foam cells is inhibited. Therefore, the macrophage Angulin-1 can be used as an atherosclerosis drug target, a gene therapy target gene and an auxiliary diagnosis marker, and a new theoretical basis and an intervention strategy are provided for prevention and treatment of the disease.

The invention discloses an antibody-modified lipid nanoparticle, a preparation method thereof and application of the antibody-modified lipid nanoparticle as a targeting carrier. The invention provides lipid nanoparticles coupled with an antibody and loaded with nucleic acid. The lipid nanoparticles are characterized in that raw materials of the lipid nanoparticles consist of ionizable lipid, phospholipid, steroidal lipid, PEG lipid and PEG-Mal lipid, the PEG lipid is C16-PEG2k, and the PEG-Mal lipid is C16-PEG2k-Mal, and the PEG-Mal lipid is C16-PEG2k-Mal. The method aims at the key scientific problems of low delivery efficiency, insufficient targeting and the like in the field of in-vivo hematopoietic stem / progenitor cell gene therapy at present. The invention develops a lipid nanoparticle delivery system based on antibody modification, provides a modular antibody targeted delivery platform with high universality, and shows huge clinical transformation potential.

The disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising one or more chemically modified nucleobases. In some embodiments, the dsDNA molecule is circular and comprises a first strand and a second strand, wherein the first strand comprises one or more chemically modified nucleobases, and the second strand is free of chemically modified nucleobases. In some embodiments, the dsDNA molecule comprises a promoter sequence and an effector sequence that encodes an effector.

The present invention relates to the field of genetic engineering. Specifically, the present invention relates to cytosine deaminase and use thereof in base editing. More specifically, the present invention relates to a base editing system based on a newly identified cytosine deaminase, a method for base editing a target sequence in the genome of an organism (e.g., a plant) using the base editing system, and a genetically modified organism (e.g., a plant) produced by the method and progenies thereof.

The invention belongs to the technical field of gene editing, and discloses a base editor system and application. According to the invention, a heterologous peptide sequence is inserted into IscB protein, the obtained peptide embedded IscB is fused with deaminase or glycosylase to construct a base editor, and DNA base editing is carried out. According to the base editor system, the size limitation is overcome, and single AAV delivery is achieved; the editing efficiency is obviously improved; the broad-spectrum applicability is realized; the system optimization is more flexible; the method has efficient editing potential in vivo, and the off-target effect is reduced. The invention provides an important new strategy for hyperlipemia treatment and provides a basis for gene therapy of other hereditary diseases.

A printed circuit board according to an embodiment comprises: an insulating layer; a circuit pattern disposed on the upper surface of the insulating layer; a support layer which is disposed on the upper surface of the insulating layer to expose the upper surface of the circuit pattern and is in contact with the sides of the circuit pattern; and a protective layer disposed on the upper surfaces of the support layer and the circuit pattern, wherein the upper region of the insulating layer comprises a first region and a second region, and the protective layer comprises an open region exposing the upper surfaces of the support layer and the circuit pattern that are disposed in the first region, and the support layer comprises a first upper surface positioned at the highest level among the upper surfaces of the support layer and a second upper surface positioned at the lowest level among the upper surfaces of the support layer, the second upper surface being lower than the first upper surface, and the protective layer comprises a first portion which contacts the upper surface of the circuit pattern of the first region and a second portion which contacts the upper surface of the support layer of the first region, and the second portion of the protective layer contacts the second upper surface of the support layer and includes a first lower surface which is lower than the upper surface of the circuit pattern.

The invention discloses an application of core proteoglycan or a coding gene thereof as a target spot in preparation of psoriasis treatment drugs, and a series of experiments prove that DCN can effectively protect mouse psoriasis-like dermatitis induced by imiquimod, improve skin scale, erythema, thickening and epidermal abnormal differentiation, enhance the barrier function of skin, improve the curative effect of psoriasis, and improve the curative effect of psoriasis. A large amount of infiltration of inflammatory cells is reduced, and a certain anti-inflammatory effect is achieved. Experimental research shows that the DCN has an obvious drug effect on a psoriasis model, is safe and efficient, has no side effect, is simple in production process and has the potential of realizing medical transformation. And the potential application value of the DCN on other various skin inflammatory diseases can be expanded.

In some aspects, the present disclosure provides compositions comprising an inhibitory polynucleotide and either a guide polynucleotide and / or a polynucleotide that encodes for a nuclease or a nuclease; and a lipid nanoparticle comprising at least one ionizable lipid; wherein the each of the nucleic acids are encapsulated within the lipid nanoparticle, and pharmaceutical compositions thereof. The present disclosure also provides methods employing said compositions and / or pharmaceutical compositions, such as methods of treating diseases or disorders.

The invention relates to an application of an intervention SNRK-MTA1 signal channel axis in preparation of a non-small cell lung cancer targeted therapy drug. The nucleotide sequences of the mRNA of the SNRK gene and the mRNA of the MTA1 gene are respectively as shown in SEQ ID NO.1-2. The invention innovatively provides a strategy for treating the non-small cell lung cancer through double-target combined intervention. According to the strategy, SNRK gene expression is improved through exogenous gene overexpression plasmids, and meanwhile MTA1 gene expression is silenced through the siRNA technology. In a non-small cell lung cancer model, the strategy of combined application of the SNRK-OE plasmid and siMTA1 can specifically up-regulate the SNRK mRNA level and knock down the MTA1 mRNA level at the same time, and the combined strategy shows a better anti-tumor effect than single intervention, and can more effectively inhibit the growth and migration of tumor cells. Based on the discovery, the SNRK-MTA1 signal pathway axis can be developed into a novel therapeutic target for non-small cell lung cancer, and is used for designing a drug combination scheme or a composite targeted drug.

Aspects of the disclosure relate to complexes comprising an anti-TfR1 antibody covalently linked (e.g., via a linker such as a peptide linker) to a lysosomal enzyme (e.g., an acid alpha glucosidase enzyme), and methods of making and using the fusion complexes to treat a lysosomal storage disease (e.g., Pompe disease).

The present disclosure provides materials and methods for delivery of a transgene to target cells. The regulatory elements, transgenes, and expression vectors are useful in, e.g., expressing a transgene in CNS cells that results in an improvement in at least one symptom related to a neurological disease or disorder, including epilepsy disorders, such as refractory epilepsy.

Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and / or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

Provided herein are methods of inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a cell or a population of cells in a subject, methods of expressing a polypeptide of interest from a target genomic locus in a cell or a population of cells in a subject, methods of treating an enzyme deficiency in a subject in need thereof, and methods of preventing or reducing the onset of a sign or symptom of an enzyme deficiency in a subject in need thereof. The methods use CD40 inhibitors (e.g., CD40 antigen-binding molecules) to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting.

The invention discloses application of PGRN in preparation of products for preventing and treating neuropsychiatric disorder related diseases caused by estrogen deficiency. The invention provides an application of a PGRN protein or a coding gene thereof or a virus expressing the coding gene thereof in preparation of a product with any one of the following functions: 1) preventing or treating or saving neuropsychiatric disorder related diseases caused by estrogen deficiency; 2) preventing or treating perimenopausal anxiety and / or depression symptoms; and 3) relieving anxiety-like behaviors and / or depression-like behaviors caused by estrogen deficiency. The application proves that the PGRN can play a role in protecting neuron damage caused by estrogen deficiency by rescuing CTSD enzyme activity and an autophagy pathway, and prompts that related medicines and measures influencing secretion and content of the PGRN can treat perimenopausal anxiety and depressive symptoms; and a new target and a new idea are provided for clinical treatment and drug development of anxiety and depression symptoms of climacteric women.

The invention discloses PROTAC capable of efficiently degrading a target protein and a preparation and delivery method of the PROTAC, a phase separation sequence and a designed double-targeting molecule are fused to respectively target the target protein and a proteasome, and phase separation of the PROTAC and the target protein is realized, so that efficient degradation of the target protein is realized. In addition, the delivery of PROTAC is also realized by encapsulating mRNA with LNP, and the target protein can also be efficiently degraded in cells, so that a way is also provided for the delivery of peptide or protein PROTAC into the human body.

The invention relates to the technical field of biotechnology and gene function and application, and provides application of SNHG8 in preparation of drugs for preventing and treating non-alcoholic fatty liver diseases. The medicine is used for preventing and treating the non-alcoholic fatty liver disease by promoting SNHG8 gene expression. The SNHG8 is applied to preparation of the medicine for preventing and treating the non-alcoholic fatty liver disease, the medicine can effectively reduce the content of triglyceride in the liver by promoting SNHG8 gene expression, liver lipid accumulation increase and lipid metabolism related protein expression up-regulation induced by high-fat and high-cholesterol diet are relieved, and therefore the non-alcoholic fatty liver disease is prevented, treated or relieved. The purpose of preventing and treating the non-alcoholic fatty liver disease is achieved.

Provided herein are methods of inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a cell or a population of cells in a subject, methods of expressing a polypeptide of interest from a target genomic locus in a cell or a population of cells in a subject, methods of treating an enzyme deficiency in a subject in need thereof, and methods of preventing or reducing the onset of a sign or symptom of an enzyme deficiency in a subject in need thereof. Some methods, such as when a subject has preexisting against an immunogen to be administered, use plasma cell depleting agents or combinations comprising plasma cell depleting agents to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting. Other methods, such as when a subject has no preexisting immunity against an immunogen to be administered, use B cell depleting agents (e.g., anti-CD20xCD3 antibody or functional fragment thereof) to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting.

The invention discloses an application of a compound in preparation of a product for enhancing the metabolic activity of hematopoietic stem cells and treating metachromatic white matter dystrophy. The compound comprises Azoramide. Azoramide is adopted to treat transfected hematopoietic stem cells, and cell apoptosis, cell necrosis and mitochondrial respiration conditions of the hematopoietic stem cells are obviously improved, so that the hematopoietic stem cells are expected to be applied to enhancement of transfection efficiency and metabolic activity of the hematopoietic stem cells transfected by the ARSA gene and reduction of ROS generation, and the effectiveness of the hematopoietic stem cells in treatment of MLD diseases is enhanced.

The invention relates to application of an MYZAP overexpression recombinant vector in preparation of a medicine for preventing and treating arrhythmia, and belongs to the technical field of biological medicines. In order to solve the problem that application of gene drugs in prevention and treatment of arrhythmia after myocardial infarction is limited, the invention provides application of a myocardial microbelt adhesion protein MYZAP overexpression recombinant vector in preparation of drugs for prevention and treatment of arrhythmia, and the MYZAP overexpression recombinant vector is an adeno-associated virus vector AAV9-MYZAP of an overexpression MYZAP gene. In-vivo experiments prove that MYZAP overexpression can reduce the occurrence of arrhythmia after myocardial infarction by increasing the content of MYZAP protein in cardiac myocardial cells, and improve cardiac functions and cardiac electrical conduction disorders after myocardial infarction. On the basis, the invention further provides a medicine for preventing and treating arrhythmia after myocardial infarction, a new strategy is provided for gene therapy of arrhythmia after myocardial infarction, and the medicine has a wide clinical application prospect.

The present disclosure provides codon optimized GBA1 polynucleotides encoding a GCase protein, wherein a portion of the coding sequence deviates from the wild type. The disclosure also provides expression constructs, vectors, viral particles or compositions containing the disclosed polynucleotides. In addition, methods and uses of these polynucleotides, expression constructs, vectors, viral particles or compositions are also provided, including the treatment of diseases or conditions associated with GCase deficiency.

Among other things, the present disclosure provides oligonucleotides, compositions and methods thereof that are useful for adenosine modification. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine modification.

The invention relates to the field of gene engineering. In particular, the present invention relates to cytosine deaminases and their use in base editing. More specifically, the invention relates to a method for screening and identifying a deaminase, a base editing system based on a newly identified cytosine deaminase, a method for editing a target sequence in a genome of an organism (such as a plant) by using the base editing system, and a method for screening and identifying the target sequence. As well as genetically modified organisms (e.g., plants) and progeny thereof produced by the method.

A polyphenol modified vector, a gene delivery system, and the use thereof in preparing a gene drug. The polyphenol modified vector comprises a vector and a polyphenol modifying same. The gene delivery system comprises the polyphenol modified vector and a gene loaded on the polyphenol modified vector.