3056results about "Active genetic ingredients" patented technology

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 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.

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.

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).

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.

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.

This invention provides vectors (e.g., lentiviral vectors) and expression cassettes for incorporation into vectors for expressing an alpha-globin (α-globin) gene. In certain embodiments method of treatment using such vectors are provided.

The present disclosure relates to novel adeno-associated adenovirus (AAV) vectors comprising targeting peptides. More particularly, the present disclosure relates to an adeno-associated serotype 2 virus vector, AAV2, comprising a transgene encoding LIGHT wherein the viral capsid of the AAV2 vector comprises a targeting peptide that alters its tropism to target tumor endothelial cells; and a use of the carrier. The disclosure also relates to the use of said vectors in therapy, in particular in the treatment of cancer.

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 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.

Disclosed is a composition for treating dystrophic epidermolysis bullosa, the composition containing, among other things, a composition which includes cells that are derived from the lesions of dystrophic epidermolysis bullosa patients and that have been genetically engineered such as to produce type VII collagen.

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.

Aspects of the disclosure relate to bicistronic AAV nucleic acid constructs comprising a transgene encoding hexosaminidase A (HEXA) and hexosaminidase (HEXB) proteins. In some embodiments, the disclosure provides methods for treating or preventing lysosomal storage disorders, such as Tay-Sachs disease and Sandhoff disease, using bicistronic nucleic acid constructs described by the disclosure.

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

The present disclosure relates to a CCL20 promoter derived from a regulatory region of the CCL20 gene, which stimulates gene expression in response to inflammation. These CCL20 promoters, which can be stimulated by endogenous or exogenous cytokines, can be used to control the timing of expression of heterologous genes. The disclosure also relates to expression cassettes or vectors comprising a CCL20 promoter of the disclosure operably linked to a nucleic acid sequence encoding, for example, a polypeptide of interest; and delivery systems (e.g., viral particles, lipid vesicles or nanoparticles) or cells comprising such expression cassettes or vectors. The disclosure also relates to the use of the promoter, expression cassette, vector, delivery system or cell in the treatment of inflammation-related diseases or for recombinant gene expression.

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.

The disclosure provides, for example, a DNA molecule comprising a first strand of DNA, wherein the first strand is circular and single stranded over at least 90% of its length, and a second strand of DNA covalently linked to the first strand as described herein. The DNA molecule may comprise an effector sequence encoding a therapeutic effector. In some embodiments, the DNA molecule shows improved conversion to double-stranded DNA relative to a DNA molecule that lacks the second strand.

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 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 invention provides sgRNA for knocking out zebra fish pde6a and application of the sgRNA in visual diseases. According to the sgRNA provided by the invention aiming at a specific position, pde6a of the zebra fish can be knocked out or knocked down in a targeted manner by utilizing a CRISPR / Cas9 system. After pde6a is successfully knocked out or knocked down, a zebra fish model with impaired visual functions and normal retina development is obtained, and the model also has morphological changes such as shorter body length, smaller eyes and shorter inter-ocular distance and also shows a trend of increasing the length of an ocular axis. The zebrafish model provides an experimental tool and a model basis for the research of visual function related diseases.

Aspects of the disclosure relate to recombinant gene editing complexes comprising a recombinant gene editing protein and guide RNA (gRNA) that specifically hybridizes to a region of a C90RF72 gene (e.g., a region flanking a G4C2 repeat or within a exonic region of the gene).

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.

The present invention features compositions and methods for editing genes associated with Shwachman-Diamond Syndrome (SDS) using programmable nucleobase editors (e.g., to provide splice sites and / or alter nonsense mutations) so that the genes are transcribable and produce a functional gene product.

The invention belongs to the technical field of gene engineering and cell transformation, and discloses a gene engineering construction method and application of anti-apoptosis human mesenchymal stem cells. Through HDAC1 K412 site specific lactic acid mutation, breakthrough improvements are realized: for example, CRISPR-Cas9-mediated accurate gene editing is utilized, only a single amino acid site is changed, that is, K412R mutation simulates persistent lactic acid, and whole genome apparent modification disturbance can be avoided; the modification does not depend on an exogenous metabolic substrate, and the negative feedback effect of traditional metabolic intervention is overcome; the mutant continuously inhibits a P53 apoptosis pathway, so that the oxidative stress mediated apoptosis resistance of the MSC is remarkably improved. According to the design concept of one target spot and one regulation, the core contradiction that long-term effectiveness and specificity cannot be considered in the prior art is fundamentally solved, and a brand new normal form is provided for stem cell treatment.

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.