5644results about "Gene therapy" patented technology

The invention provides a production strain of an antibiotic-free plasmid, the production strain is a gene editing strain of a PIR strain and is named as PIR1-WN:: 0636 or PIR1-PR: 0636, the production strain contains a nucleotide sequence for coding toxin protein and the antibiotic-free plasmid, and the antibiotic-free plasmid contains a nucleotide sequence for coding antitoxin protein; and preferably, the replicon DNA element of the nonreactive plasmid is R6K-gamma. The toxin protein gene of the production strain disclosed by the invention can be stably passaged, has lethality after being induced and can be used for plasmid screening; according to the invention, the positive rate of transforming the nonreactive plasmid into the PIR1-WN:: 0636 strain is more than 80%, and stable production of the plasmid with a high superhelix ratio can be realized.

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 a lipid compound capable of being used for gene delivery, a preparation method of the lipid compound and application of the lipid compound in gene delivery. Also disclosed herein is a lipid nanoparticle comprising the lipid compound, a gene delivery composition comprising the lipid compound or the lipid nanoparticle. The lipid compounds, lipid nanoparticles and delivery systems herein enable efficient complexation, protection, intracellular and targeted delivery and release of biomolecules, such as oligonucleotides and nucleic acids, in vitro and in vivo tissues and organs.

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.

The present invention provides, among other things, improved pharmaceutical compositions comprising codon-optimized mRNA encoding a peptide or polypeptide encapsulated in a lipid nanoparticle comprising one or more of the cationic lipids that are particularly effective for pulmonary delivery.

Described herein are targeting moieties that can be capable of specifically targeting muscle cells and can include an n-mer motif. In some embodiments, the n-mer motif contains an RGD motif. Also described herein are vector systems, particles, polypeptides that can encode and / or contain one or more targeting moieties. Also described herein are methods of delivering a cargo to a cell, such as a muscle cell, using one or more of the targeting moieties described herein.

The present invention relates to a novel lipid compound for tissue-specific delivery, and a lipid nano-particle (LNP) composition comprising the same, the lipid nano-particle comprising a modified lipid compound as a component, according to the present invention, internal active substances are selectively delivered into cells of specific tissues such as lymph nodes, spleen, retina, cancer, brain, liver and the like in vivo, thereby preventing side effects and safely exhibiting a desired level of effect. The tissue-specific non-viral LNP delivery vectors can be effectively used for prevention of infectious diseases and treatment of rare and refractory (hereditary) diseases (diseases which are effectively and selectively delivered to in-vivo targeted sites, such as macular degeneration, diabetic retinal degeneration, hereditary retinal degeneration, cancer, cerebral diseases, liver diseases and the like).

Methods to edit genes by administering a chimeric nuclease to a cell or organism without the use of a viral vector.

Provided herein are methods and related compositions for enhancing or enhanced partial reprogramming of target cells in a subject in need thereof (e.g., a human subject suffering from or at risk of a disease), the method comprising administering a plurality of mesenchymal lineage progenitor or stem cells (MLPSCs), exosomes derived therefrom, or conditioned culture media derived therefrom to a subject that expresses or will express one or more reprogramming factors in a population of target cells, whereby a plurality of the target cells in the subject become partially reprogrammed, but not fully reprogrammed.

The invention relates to a gene, a protein and a plasmid of a trachinotus ovatus apoptosis regulatory factor Bok and application of the gene, the protein and the plasmid, and belongs to the field of molecular biology, the sequence of cDNA nucleotide of the trachinotus ovatus apoptosis regulatory factor Bok is as shown in SEQ ID NO.1, and the amino acid sequence is as shown in SEQ ID NO.2. The invention further provides a construction method of the eukaryotic expression plasmid of the trachinotus ovatus apoptosis regulatory factor Bok. The regulation effect of the constructed eukaryotic expression vector on other apoptosis-related factors of the trachinotus ovatus is verified, and after the eukaryotic expression plasmid for the apoptosis regulation factor Bok of the trachinotus ovatus is injected into a fish body, the disease resistance of the fish body can be remarkably improved, and a remarkable immune protection effect is achieved.

The invention provides an RNP compound, an electrotransfection composition and a pharmaceutical composition thereof, a CD34 + cell gene editing method using the composition, and a method for obtaining HBG gene target mutation in a CD34 + cell genome.

The present invention provides a method for producing nucleic acid-encapsulating lipid nanoparticles, including the following steps (a) and (b): step (a) of mixing an alcohol solution containing an ionic lipid having a tertiary amino group, a sterol, and a PEG lipid with a citrate buffer having pH 3 to 6.5 in which nucleic acid is dispersed to prepare a suspension of nucleic acid-encapsulating lipid nanoparticles; and step (b) of exchanging a dispersion medium of the aforementioned suspension for a Tris buffer having pH 5.2 to 9.0 by concentrating the suspension of nucleic acid-encapsulating lipid nanoparticles by ultrafiltration and diluting same with the aforementioned Tris buffer.

The invention relates to an STING gene knockout TIL capable of enhancing anti-tumor activity and a preparation method and application of the TIL, in particular to a genetically engineered immune cell, and an STING gene in the genetically engineered immune cell is silenced or down-regulated. The ferroptosis resistance of the immune cell provided by the invention is remarkably enhanced, the immune cell can be better infiltrated into a tumor microenvironment, and the immune cell has a remarkable anti-tumor effect.

The invention discloses a recombinant adeno-associated virus vector for targeted delivery of VEGF-C (vascular endothelial growth factor-C) and application of the recombinant adeno-associated virus vector in promoting endocardial differentiation to treat coronary heart disease. The rAAV vector comprises transgene for coding VEGF-C protein or VEGF-C protein functional variant and a tissue-specific promoter operably connected to the transgene, wherein the tissue specific promoter is capable of driving the transgene to be specifically expressed in the heart endothelial cells. According to the treatment method developed by the invention, specific expression of the Vegfc gene in the heart is driven by using an ICAM2 promoter with targeting to endothelial cells, and a remarkable curative effect is shown in a myocardial infarction model mouse. The therapeutic scheme provides a new effective strategy for intervention and treatment of myocardial infarction and chronic heart failure, and has the advantages of high safety, long gene expression duration, extremely low immune response to a host and the like.

The disclosure is directed in part to variant capsid polypeptides that can be used to deliver payloads.

Lipid nanoparticle compositions for the delivery of nucleic acids are provided.SOLUTION: In various embodiments, the lipid nanoparticle comprises an ionizable lipid of Formula (I). Also provided are methods of using such lipid nanoparticle compositions to achieve targeted delivery of therapeutic cargo without the need for a targeting ligand.SELECTED DRAWING: None

The present invention relates to engineered liver-specific core promoters, synthetic promoters (which contains the engineered core promoters and enhancers), expression vectors (which contains the synthetic promoter), as well as methods of using the promoter or the expression vector thereof to address the need in the field, including treatment of various genetic diseases or conditions associated with the liver. In some embodiments, the liver-specific promoter includes continuous or discontinuous genome sequences from SERPINA1 genome.

The invention discloses nano-enzyme coating recombinant probiotics as well as a preparation method and application thereof, and belongs to the technical field of biotechnology and nano medicine. According to the invention, engineered Escherichia coli Nissle 1917 (ECN (DE3)) is taken as a host, and glutathione peroxidase (GPX) and glutathione reductase (GR) genes are over-expressed through a genetic engineering means, so that an efficient antioxidant enzyme system is constructed. And sequentially modifying chitosan and cerium dioxide nano-enzyme (CNP) on the surfaces of the thalli by using an electrostatic layer-by-layer self-assembly technology to form a protective coating. The nano-enzyme coating significantly improves the survival rate of the recombinant probiotics in severe environments such as simulated gastric acid (pH 2.5) and bile salt (0.3%), and enhances the ability of the recombinant probiotics to remove reactive oxygen species (ROS), including hydrogen peroxide, superoxide anions, hydroxyl free radicals and DPPH free radicals.

Provided herein are modified nucleic acids comprising modified MTM1 genes, modified muscle-specific promoters, e.g., MHCK7, or a combination thereof. Also provided herein are expression cassettes, AAV vector genomes, and AAV particles comprising the same. Further provided herein are methods of delivering MTM1 to a muscle cell and methods of treating XLMTM.

The invention relates to the technical field of medicines, and discloses an adeno-associated virus (AAV) injection carrying an artificial chemical genetics receptor gene sequence, and a combinatorial chemical genetics scheme formed by the adeno-associated virus injection and a small molecule agonist quetiapine. Compared with the traditional chemical genetics, the medicine quetiapine with smaller clinical side effect is used as the activating agent for the first time, and a novel chemical genetics system with lower medication risk is developed. The system can effectively reduce the excitatory activity of neurons, avoids the medication risk caused by clozapine or other non-market traditional chemical genetics activators, and improves the feasibility of clinical transformation of the chemical genetics system. In the aspect of application of a novel or traditional chemical genetics system, the combined treatment scheme is applied to intervene in Parkinson's disease (PD) for the first time, abnormal activities of STN and related loops of PD patients can be inhibited, and the dyskinesia symptom can be remarkably improved.

A gene editing protein variant is capable of reducing a gene editing off-target rate. The variant is an unnatural protein with cis-cleavage activity, and the variant has reduced trans-cleavage activity as compared to a wild-type gene editing protein thereof. Furthermore, the variant is mutated at one or more of cleavage activity-related core amino acid sites of the wild-type gene editing protein selected from the following: a phenylalanine (F) site corresponding to the 1081st position of FnCas12a; and / or a lysine (K) site corresponding to the 1069th site of the FnCas12a. The variant can have cis-cleavage activity and reduced trans-cleavage activity. Moreover, the gene editing protein variant or a gene editing system having the gene editing protein variant can significantly reduce the gene editing off-target rate.

Methods of treating a subject for a dissociative disorder and methods of screening agents for the ability to modulate dissociative and associative states in a subject are provided. In particular, agents that alter rhythmic neural activity in the posteromedial cortex can be used to modulate dissociative and associative states in a subject.

Several embodiments relate to methods of repairing and / or regenerating damaged or diseased tissue comprising administering to the damaged or diseased tissues compositions comprising exosomes. In several embodiments, the exosomes comprise one or more microRNA that result in alterations in gene or protein expression, which in turn result in improved cell or tissue viability and / or function.

According to various aspects of this disclosure, the present disclosure relates to methods for reducing kidney inflammation, reducing kidney fibrosis, reducing oxidative stress in the kidney, preventing or reducing the likelihood of chronic kidney disease (CKD), treating or preventing acute kidney injury (AKI) or treating a kidney disease in a subject in need thereof comprising administering, e.g., intramuscularly, to the subject a recombinant adeno-associated virus (rAAV) vector, wherein the rAAV vector comprises a vector genome comprising a nucleotide sequence encoding a Fibroblast growth factor 21 (FGF21) or a functional fragment thereof and an AAV capsid (e.g., AAV1 serotype), optionally, wherein the subject does not suffer from diabetes.

The present invention relates to a compound represented by formula (I) or a stereoisomer, tautomer, solvate or pharmaceutically acceptable salt of a compound represented by formula (I), TIFF2026503201000033.tif3981X1, X2 and X3 are each independently an optionally substituted C1-C 15 alkylene, and R and R are each independently an optionally substituted C-C 40 Alkyl, optionally substituted C-C 40 Heteroalkyl, optionally substituted C-C 40 Alkenyl, optionally substituted C-C 40 Heteroalkenyl, optionally substituted C-C 40 Alkynyl or optionally substituted C-C 40 The present invention provides a compound comprising heteroalkynyl, wherein R3, R4, R5, and R6 are each independently H, halogen, or optionally substituted C1-C3 alkyl, and the substituents are independently selected from halogen, -OH, -SH, -NH2, -NO2, cyano, and C1-C3 alkyl, which has the advantages of low cytotoxicity, strong delivery ability, and strong immunostimulatory effect.

Compounds and compositions capable of modulating immune responses in patients, as well as implantable elements containing them, are provided. [Solution] For example, 4-((1-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methyl)thiomorpholine 1,1-dioxide, as well as pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives and compositions thereof, and implantable elements (e.g., devices and materials) containing these are provided.

The present invention provides an adeno-associated virus (AAV) vector gene therapy for use in treating a monogenic form of nephrotic syndrome, wherein the AAV vector comprises a NS-associated transgene and minimal nephrin promoter NPHIS1 or podocin promoter NPHIS2.

The present invention relates to the field of non-viral vectors and pharmaceutical compositions comprising polypropyleneimine and nucleic acids, and their use in human or veterinary medicine. More particularly, the present invention relates to pharmaceutical compositions comprising polypropyleneimine polymers or copolymers for the delivery or transfection of nucleic acids, such as RNA. The pharmaceutical compositions described herein are particularly useful for (nucleic acid) vaccination, nucleic acid-based protein therapy, nucleic acid-based protein replacement therapy, gene editing, base editing, cell therapy, immunotherapy, stem cell therapy, regenerative medicine, gene silencing, nucleic acid inhibition or protein inhibition.