1345results about "Non-active genetic ingredients" patented technology

The invention relates to methods of modulating immune cells in a patient by altering microbiota of the patient. The invention also relates to methods of modulating treatments or therapies in a subject organism by altering microbiota of the subject. The invention also relates to cell populations, systems, arrays, cells, RNA, kits and other means for effecting this. In an example, advantageously selective targeting of a particular species in a human gut microbiota using guided nucleic acid modification is carried out to effect the alteration.

The invention relates to the field of gene therapy, in particular to an RBM25 gene epigenetics activation technology based on a CRISPR / dCas9-SunTag system and application of the RBM25 gene epigenetics activation technology in ischemic heart failure treatment, the RBM25 gene epigenetics activation technology comprises the following steps: (a) protein containing inactivated Cas9 (dCas9) fused with a plurality of GCN4 peptide repetitive sequences, the number of the GCN4 peptide repetitive sequences is 8-12, and the dCas9 contains D10A and H840A double mutations; (b) a protein containing fusion of an anti-GCN4 single-chain antibody fragment (scFv) and a TET1 catalytic structural domain; (c) at least one gRNA of a target RBM25 gene promoter region, wherein a target sequence of the gRNA is selected from a sequence as shown in SEQ ID NO: 1-3; and (d) a lipid nanoparticle (LNP) system for delivery of said (a), (b), and (c).

The present invention relates to peptides, in particular cell-penetrating peptides, and to conjugates of such cell-penetrating peptides with a therapeutic molecule. The present invention further relates to use of such peptides or conjugates in methods of treatment or as a medicament, especially in the treatment of genetic disorders and in particular muscular dystrophies such as Duchenne muscular dystrophy.

Disclosed herein are therapeutic applications of CRISPR / Cpf1-based genome editing.

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 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.

To provide a pharmaceutical for treating cancer.SOLUTION: The present invention provides a pharmaceutical comprising a population of modified NK-92 cells, wherein the modified NK-92 cells comprise CD16 and IL-2 and comprise a specific sequence on chromosome 17, and more than 90% of the cells in the cell population express CD56, CD16, CD54, and NKp30, and less than 5% of the cells in the cell population express CD3.SELECTED DRAWING: Figure 1

In some aspects, the disclosure relates to compositions and methods useful for inhibiting SOD1 expression in cells (e.g., cells of a subject). In some embodiments, the disclosure describes isolated nucleic acids engineered to express an inhibitory nucleic acid targeting endogenous SOD1 and an mRNA encoding a hardened SOD1 protein. In some embodiments, compositions and methods described by the disclosure are useful for treating Amyotrophic Lateral Sclerosis (ALS) in a subject.

Provided are methods for delivering lipid nanoparticles (LNPs) to a lung cell of a subject suffering from or at risk for primary ciliary dyskinesia (PCD), wherein the method comprises nebulizing a liquid pharmaceutical composition to generate an aerosolized pharmaceutical composition, and administering the aerosolized pharmaceutical composition to the subject.

The invention provides an establishment method of umbilical cord mesenchymal stem cells with high expression of IGF-1 (Insulin-like Growth Factor 1) and application of the umbilical cord mesenchymal stem cells in premature ovarian failure. The construction method of the umbilical cord mesenchymal stem cells with high expression of IGF-1 comprises the step of transfecting the umbilical cord mesenchymal stem cells with the IGF-1 gene, so that the umbilical cord mesenchymal stem cells highly express IGF-1. The invention also provides application of the umbilical cord mesenchymal stem cell with high expression of IGF-1 in preparation of drugs for treating premature ovarian failure. According to the invention, the IGF-1 gene is transfected to the hUC-MSC, so that the hUC-MSC highly expresses the IGF-1, and the hUC-MSC secretes a large amount of IGF-1. The ovarian function is improved through the immunoregulation effect of hUC-MS, and meanwhile, the effect of resisting apoptosis of granular cells is achieved through IGF-1 secreted by hUC-MS. And the treatment effect on the premature ovarian failure is achieved through synergism of the two effects.

The invention discloses an application of HuR and a coding gene thereof in preparation of a medicine for treating senile deafness, belongs to the technical field of gene engineering, and provides an application of the HuR coding gene in preparation of a medicine for preventing or treating senile deafness, and the nucleotide sequence of the HuR coding gene is shown as SEQ ID NO.1. According to the application of the HuR in preparation of the medicine for preventing or treating the senile deafness, the amino acid sequence of the HuR is shown as SEQ ID NO.2. The invention discovers the application of HuR in preventing or treating age-related hearing loss for the first time. The HuR coding gene is packaged by an adeno-associated virus (AAV) and then is injected into the inner ear through a round window, so that the HuR coding gene is widely overexpressed in various cells of the inner ear, the occurrence of the senile deafness can be resisted or delayed, and a theoretical basis is provided for clinically preventing and improving the hearing loss of a patient with the senile deafness.

The invention provides a targeting vector and a method for targeting a host cell, the vector comprises a first molecule combined with an endocytosis receptor of a target cell and a second molecule for promoting release of a substance carried by the targeting vector into cytoplasm, when the targeting vector is a virus vector, the first molecule is not a part of a virus envelope protein, and the second molecule is not a part of a virus envelope protein. The second molecules promote endosome escape or lysosome escape of the targeting carrier. According to the present invention, the first molecule is designed according to the endocytosis receptor of the to-be-targeted cell so as to target different types of cells, and after the vector is subjected to reasonable mutation, the infection of the cells not requiring the targeting can be avoided, and the accuracy of the vector can be improved.

The invention discloses a VpCas9 protein, a single site mutant of the VpCas9 protein and application of the VpCas9 protein in gene editing. According to the invention, mining and modification of Cas9 are carried out through a deep learning model, new Cas9 protein VpCas9 protein is finally obtained through screening, and the amino acid sequence of the Cas9 protein VpCas9 protein is shown as SEQ ID No.5; compared with the SpCas9 protein, the VpCas9 protein has a better editing effect in the aspects of gene editing efficiency, PAM compatibility or specificity and the like; according to the invention, single site mutants with higher editing efficiency are further obtained through sequence screening and optimization design, and compared with SpCas9 protein and VpCas9 protein, the single site mutants have a better gene editing effect in genome editing; the VpCas9 protein and the single site mutant thereof provided by the invention have application prospects in genome editing or target nucleic acid editing of plants, animals or microorganisms.

The invention belongs to the field of gene engineering. Specifically, the invention relates to a base editing system for optimizing engineered T cells and application of the base editing system. The present invention provides a base editing system for modifying engineered T cells, comprising: i) a base editing polypeptide, and / or an expression construct encoding a base editing polypeptide, the base editing polypeptide comprising a DNA binding protein and at least one deaminase domain; ii) a guide RNA, and / or an expression construct encoding a guide RNA, the guide RNA targeting any one of TRAC, TGFBR2, PD-1, CISH, and / or FAS genomic regions, or any combination thereof. The base editing system disclosed by the invention has high efficiency of a gene editing tool and low Indel frequency, can realize accurate editing of T cell function enhancement related genes, and has important value for expanding application scenes of a base editing technology in the fields of preparation of safe and efficient engineered T cells and the like.

Recombinant adenovirus genomes that include an exogenous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. Optimal placement of the exogenous genes for minimal impact on viral kinetics is further disclosed. Therapeutic applications of the recombinant adenoviruses are also described.

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 present invention relates to a viral gene therapy vector for removing hepatitis B viruses, a preparation method therefor, and the use thereof, aiming to solve the problem in which existing viral gene therapy vectors can only inhibit the replication of hepatitis B viruses, but cannot remove virus cccDNA. The vector comprises a promoter, an intron, an enhancer, a nuclear localization signal (NLS) functional domain encoding gene of PGLYRP2 protein, an HBV DNA binding domain encoding gene of the PGLYRP2 protein, a secretory signal peptide functional domain encoding gene of the PGLYRP2 protein, an HBV nucleocapsid-binding functional domain encoding gene of the PGLYRP2 protein, and an IRES fragment. The viral gene therapy vector can remarkably promote the removal of HBVs in the liver of mice and is used for treatment of hepatitis B virus infection.

The invention discloses a VpCas9 protein double-site mutant and an application of the VpCas9 protein double-site mutant in gene editing. The invention firstly provides a homologue VpCas9 protein of Cas9, the amino acid sequence of the homologue VpCas9 protein is shown as SEQ ID No.5, and compared with SpCas9, the homologue VpCas9 protein has a better editing effect in the aspects of gene editing efficiency, PAM compatibility or specificity and the like; in order to further improve the gene editing effect of the VpCas9 protein in genome editing, the VpCas9 protein is subjected to double-site mutation, the VpCas9 protein double-site mutant is obtained, and compared with SpCas9 protein or VpCas9 protein, the VpCas9 protein double-site mutant has a better gene editing effect in genome editing, and the gene editing effect of the VpCas9 protein is improved. The method has an important application prospect in genome editing of plants, animals or microorganisms.

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.

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.

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.

The present invention belongs to the field of biotechnology, and discloses capsid protein mutants and applications for improving AAV virus yield and whole-eye infection ability. Capsid protein mutants are obtained by replacing amino acids 561 to 588 of wild-type AAV2 virus capsid protein with specific polypeptides. Capsid protein mutants of some examples of the present invention can effectively improve the whole-eye infection ability of AAV2, fundamentally solving the problem of AAV2 eye infection efficiency. Capsid protein mutants of some examples of the present invention have better yield. Capsid protein mutants of some examples of the present invention can be well applied to gene therapy of the eye or construction of eye disease models.

The invention belongs to the field of gene engineering. Specifically, the invention relates to a system, a tool and a method for modifying or editing target nucleotide bases, and more specifically, the invention relates to an optimized QBE base editing system and application thereof. The base editing system disclosed by the invention has the advantages of high efficiency of a gene editing tool, high product purity, low Indel frequency, low off-target frequency and abundant gene editing windows, and has important value for expanding application scenes of a base editing technology in the fields of life science basic research, agriculture, biological medicine and the like.

To provide novel transduction enhancers and uses thereof.SOLUTION: The present invention relates to a method for transducing a target cell, the method comprising the step of contacting a target cell with a retroviral vector and a compound capable of enhancing transduction efficiency or a combination of such compounds, wherein the target cell is pre- and / or co-stimulated by pre- and / or co-incubation with a transduction enhancing compound or a combination of transduction enhancing compounds prior to and / or during contacting the target cell with the retroviral vector.SELECTED DRAWING: None

To provide cationic lipids for delivery of oligonucleotides, where the cationic lipids can provide high drug:lipid ratios, protect a nucleic acid from degradation and clearance in serum, be suitable for systemic delivery, and provide intracellular delivery of the nucleic acid. where the cationic lipids are well-tolerated and provide an adequate therapeutic index, such that patient treatment at an effective dose of the nucleic acid is not associated with significant toxicity and / or risk to the patient.SOLUTION: The present invention relates to cationic lipids having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.SELECTED DRAWING: None

The invention relates to the technical field of biological materials, and particularly provides a plant-bacterium hybrid outer vesicle composite hydrogel microneedle as well as a preparation method and application thereof. The plant-bacterium hybrid outer vesicle composite hydrogel microneedle provided by the invention comprises a needle tip loaded with plant-bacterium hybrid outer vesicles (GBEVs-pVEGF) and a substrate containing an antibacterial material nano silver (AgNPs). After the microneedle penetrates through necrotic tissue on the surface of a diabetic wound surface, the needle point of the microneedle can quickly release the GBEVs-pVEGF, after the GBEVs-pVEGF is taken by cells, the anti-oxidation effect is achieved, meanwhile, shuttle plasmids pVEGF in the GBEVs-pVEGF are expressed by the cells to be VEGF protein, and therefore angiogenesis is promoted. In addition, a physical protection barrier formed by the composite microneedle substrate and AgNPs have a synergistic effect, and the problem of bacterial infection in the wound healing process is solved. The composite microneedle system integrates the characteristics of oxidation resistance, angiogenesis and antibiosis, effectively recovers the damaged wound surface microenvironment, and remarkably accelerates the healing of the refractory wound surface of diabetes mellitus.

Provided herein are methods to treat various neurodegenerative disorders comprising delivering a viral particles to the whole brain, including both superficial and deep structures. In some aspects, the viral particles are administered at low dose levels to the CSF, in conjunction with microbubbles followed by application of focused ultrasound (FUS) to a region of interest of the brain, thereby causing entry of the viral particles to the brain.

The present disclosure provides engineered capsid proteins and recombinant adeno-associated virus (rAAV) virions with an engineered capsid protein. In particular, the disclosure provides AAV9 virions with engineered AAV9 capsid, AAV5 / 9 chimeric capsid, or combinatory capsid that achieves increased transduction efficiency in heart, increased heart-to-liver ratio, and / or other desirable properties.

This invention relates to an engineered nanovesicle for promoting hair regeneration, its preparation method, and its application. The engineered nanovesicle for promoting hair regeneration uses extruded vesicles derived from human induced pluripotent stem cells as a carrier, and the extruded vesicles are loaded with siGroups, including siTGF-β1, siLats1, and siSFRP1. The nucleotide sequence of siTGF-β1 is 5'-CGACAAGTTGAACGCATATTGCACA-3'; the nucleotide sequence of siLats1 is 5'-CATGAACACTTTCGCTGTAAGTAAA-3'; and the nucleotide sequence of siSFRP1 is 5'-TCAAGAGACAAACACTTCGAGTGAA-3'. Compared with existing technologies, the engineered nanovesicles prepared by the method of this invention utilize extruded vesicles derived from hiPSCs as carriers to replace traditional liposome or nanoparticle treatment methods. Furthermore, the gene cargo of active molecules loaded in synergy has the characteristics of multifunctionality and good therapeutic effect, and can be used to treat the regeneration and damage repair of hair follicles in seborrheic alopecia and telogen effluvium.