1738results about "Non-active genetic ingredients" patented technology

To provide constructs, vectors, relative host cells and pharmaceutical compositions which allow an effective gene therapy, in particular of genes larger than 5Kb.SOLUTION: The present invention implements cellular large protein reconstitution by providing to a target cell two or more fragments of large protein fused to split inteins to promote intein-mediated trans-splicing and reconstitute the functional protein.SELECTED DRAWING: None

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 invention discloses a construction method and application of a gene modified mesenchymal stem cell. The construction method comprises the following steps: constructing a recombinant lentivirus carrying PD-L1 and ICAM1 genes; the recombinant lentivirus carrying the PD-L1 gene and the ICAM1 gene is transfected with mesenchymal stem cells, and the mesenchymal stem cells are screened by puromycin, so that an engineered mesenchymal stem cell strain modified by the PD-L1 gene and the ICAM1 gene is obtained; the mesenchymal stem cells provided by the invention are modified by engineering genes of PD-L1 and ICAM1, and are screened by puromycin to obtain a mesenchymal stem cell strain capable of stably and highly expressing the genes of PD-L1 and ICAM1; after the mesenchymal stem cells highly expressing the PD-L1 and ICAM1 genes are intravenously injected into an autoimmune hepatitis animal model, the autoimmune hepatitis symptom can be remarkably relieved, the liver injury degree can be reduced, the expression of inflammatory factors can be regulated, the inflammatory reaction can be inhibited, and the obvious curative effect can be achieved.

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 use of dual-target CAR-T cells in treating systemic lupus erythematosus and other B-cell autoimmune diseases is provided. The first target of the chimeric antigen receptor is CD19, the second target is BCMA, and specifically, the chimeric antigen receptor is a chimeric antigen receptor with a Loop structure, which is shown as follow: L-VL, CD19-VH, BCMA-VL, BCMA-VH, CD19-H-TM-C-CD3ζ; the BCMA-CD19 CAR-T cells transduced by the chimeric antigen receptor targeting CD19 and BCMA can completely block the pathway of producing autoantibodies, and completely cover the B cells, plasmablasts and plasma cells at multiple differentiation stages that produce autoantibodies, so that the dual-target CAR-T therapy designed based on this concept can be aimed at refractory SLE and is expected to achieve faster remission and deeper and lasting curative effect.

Disclosed herein are therapeutic targets for the correction of the human dystrophin gene by gene editing and methods of use.

The present disclosure provides compositions and methods for mRNA therapy with reduced immune reactogenicity.

The invention provides a lentivirus for treating cancer as well as a preparation method, application and a corresponding pharmaceutical composition of the lentivirus. According to the invention, an hTERT promoter and a CDC6shRNA gene sequence are inserted behind an enzyme cutting site of a vector, an obtained plasmid is transferred into an expression strain, the expression strain is cultured and screened to obtain a cloned strain, and the cloned strain is shaken and packaged to obtain the hTERT-CDC6shRNA lentivirus; when the lentivirus disclosed by the invention is used for infecting cancer cells, the experimental result shows that the proliferation of the cancer cells can be effectively inhibited.

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.

The invention belongs to the technical field of gene engineering and biology, discloses a modified adeno-associated virus AAV-8 serotype for retina wide targeting and expression, and further relates to construction and application of the modified type. 10 amino acid sequences as shown in SEQ ID NO.3 are inserted between the 590th amino acid and the 591th amino acid of an AAV-8 serotype capsid protein sequence as shown in SEQ ID NO.2, the first, second and tenth amino acids are protected amino acids, and the third to ninth amino acids are amino acid sequences obtained by screening. The modified serotype disclosed by the invention is stronger in fluorescence effect after infection and can be obviously and intuitively observed, an exogenous gene can be widely and efficiently expressed in a specific targeted tissue retina whole region, and the expression efficiency is greatly improved under the condition of using the same virus amount. And compared with a wild serotype, the serotype has better and wider targeted tissue expression and less non-targeted tissue expression.

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.

The invention discloses a cyclic IL-10mRNA nano preparation as well as a preparation method and application thereof, and belongs to the technical field of biology. The annular IL-10mRNA nano preparation is prepared by the following method: 1, synthesizing chemically modified annular IL-10mRNA in vitro, and 2, preparing the annular IL-10mRNA nano preparation capable of being delivered in vivo by a self-assembly method. The annular IL-10mRNA can regulate immune cells in synovial membranes of articular cavities and inhibit articular cartilage injury, so that the effect of treating joint inflammatory diseases is achieved. The application has the advantages that the annular IL-10mRNA is successfully delivered into the joint cavity with the joint inflammatory disease through the nano system, and the inflammation environment in the joint cavity with the joint inflammatory disease is adjusted, so that the development of inflammation is inhibited; the cyclic IL-10 promotes cartilage repair so as to improve the disease progress of joint inflammatory diseases.

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 belongs to the technical field of disease drugs, and particularly relates to application of an engineered attenuated coxsackie B3 virus vector (CVB3 (mu)) in preparation of drugs for treating traumatic craniocerebral injury. According to the application disclosed by the invention, after severe craniocerebral injury of a mouse, CVB3 (mu) can remodel a host immune system through single intraperitoneal injection treatment, so that the absorption speed of encephaledema on an affected side can be remarkably increased, and the effect of treating traumatic craniocerebral injury is achieved; in addition, the CVB3 (mu) has remarkable safety.

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 belongs to the technical field of disease drugs, and particularly relates to application of a recombinant attenuated coxsackie B3 virus loaded with an anti-inflammatory factor in preparation of drugs for treating traumatic craniocerebral injury. The virus can regulate and control a peripheral immune phenotype capable of inhibiting inflammation, after severe craniocerebral injury of a mouse, a host immune system is remodeled through single intraperitoneal injection treatment, a treatment effect is achieved in improving an immune microenvironment in the acute stage of TBI, the neuroprotective effect is observed in the early stage and the late stage of TBI, and safety is achieved.

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.