1563results about "Genetic material delivery route" patented technology

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 disclosure provides compositions and methods useful in the treatment of trinucleotide repeat disorders, including Huntington's disease and Friedreich's ataxia. The present disclosure also provides gRNAs designed to target the HTT or FXN genes. Complexes comprising a base editor and any of the gRNAs disclosed herein are also provided by the present disclosure. The present disclosure further provides polynucleotides, vectors, cells, compositions, and kits. Methods of treating Huntington's disease and Friedreich's ataxia are also provided herein.

The instant disclosure relates to lipid particles that harbor cationic lipids, the particles found to be capable of delivering associated cargoes - particularly nucleic acid cargoes when formulated as nucleic acid-lipid particles - intracellularly to skin tissue cells when administered topically to a subject. The instant disclosure provides compositions comprising such lipid particles, optionally in association with a therapeutic agent (e.g., a therapeutic mRNA and / or nucleic acid controller system), as well as methods and kits for delivering a lipid particle-associated therapeutic agent and / or for treating or preventing a disease or disorder, e.g., a skin disease or disorder, in a subject, using one or more lipid particle compositions provided herein.

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.

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 disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid protein variants.

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.

The present invention is directed to lipid nanoparticles using cationic cholesterol for topical delivery for nucleic acid delivery, and when administered locally, side effects caused by systemic drug delivery can be minimized and protein expression can be confined to the site of administration. In addition, the duration of protein expression at the site of administration can be increased, and thus the lipid nanoparticles can be useful in the technical field related to nucleic acid therapeutics.

Described herein are nucleic acid molecules, compositions, recombinant AAV (rAAV) particles, kits, and methods for delivering a base editor (or a "nucleobase editor") to a cell, for example via an AAV vector. In particular, the present disclosure provides compositions, methods and uses for delivery of adenine base editors and cytosine base editors in a single AAV vector (or genome). Further described herein are improved AAV vectors comprising a minimised size regulatory component, for example, a regulatory component that can enable packaging of a base editor. Provided herein are methods and compositions for delivering a base editor protein to a cell or tissue in a single recombinant AAV (rAAV) vector. Improved methods and compositions for in vivo delivery of these base editors in a single rAAV particle are contemplated herein. Further provided herein are base editors, and compositions and cells comprising these base editors.

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.

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.

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 disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid protein variants.

The present disclosure provides recombinant adeno-associated virus (AAV) virions with altered capsid protein, where the recombinant AAV (rAAV) virions exhibit greater ability to cross barriers between intravitreal fluid and retinal cells, and thus greater infectivity of a retinal cell compared to wild-type AAV, and where the rAAV virions comprise a heterologous nucleic acid. The present disclosure provides methods of delivering a gene product to a retinal cell in an individual.

Compositions comprising microalgal extracellular vesicles (MEVs) formulated for intranasal delivery are provided, whereby upon intranasal administration, the MEVs are transported by a specific route, to specific regions in the brain via the olfactory nerve after intranasal administration, and to interconnected brain regions through the lateral olfactory tract (LOT). The MEVs are transported via neuronal axonal transport. The MEVs have the ability to cross synapses including: (i) synapses between olfactory sensory neurons (OSNs) and mitral / tufted neurons; (ii) synapses between mitral / tufted neurons and local neurons in multiple brain regions colonized by the lateral olfactory tract (LOT); and (iii) synapses between neurons in brain regions colonized by the LOT and neurons from the frontal cortex, hippocampus, thalamus, and hypothalamus. The compositions contain extracellular vesicles (MEVs) from microalgae loaded with bioactive cargo for the treatment, detection, diagnosis, or monitoring of diseases, disorders, or conditions of or involving the brain, particularly neuronal delivery of the cargo. The compositions and methods have multiple applications as therapeutic and diagnostic agents for the treatment, diagnosis, and monitoring of diseases, disorders, or conditions of or involving the brain. The compositions can be used in methods and uses for the treatment of cancers involving the brain, and can be used, for example, to deliver therapeutic agents for psychiatric diseases, disorders, conditions, and to deliver therapeutic agents for neurodegenerative diseases, disorders, and conditions.

The invention discloses an engineered exosome for promoting hair regeneration and a preparation method and application thereof, Wnt10b gene is inserted into a plasmid vector to construct a target plasmid, the target plasmid and a lentivirus packaging plasmid are co-transfected to packaging cells to generate lentivirus particles, and then target stem cells are infected. Screening to obtain a cell strain capable of stably expressing a target gene, culturing the stably transfected strain, and collecting the engineered exosome generated by the stably transfected strain. The exosomes are rich in Wnt10b protein and can promote proliferation and differentiation of hair follicle stem cells on a molecular level, so that hair follicle tissues in a resting period are activated and enter a growing period again, and hair regeneration is realized. Meanwhile, the exosome is high in safety, and adverse reactions caused by traditional chemical synthesis drugs are avoided. The exosome can be applied to the preparation of hair regeneration products, and the accurate symptomatic treatment capability of the exosome provides a hair growth method aiming at pathogenesis for alopecia patients, and provides a new hope for patients who seek safe and effective hair growth solutions.

To provide a gene therapy vector comprising an expression cassette coding for a mammalian apolipoprotein E (APOE); a pharmaceutical composition; and a method for preventing, inhibiting or treating Alzheimer's disease in mammals.SOLUTION: The invention provides a gene therapy vector comprising an expression cassette coding for a mammalian apolipoprotein E that has a residue other than arginine at at least one of positions 112, 136 or 158, but is not a mammalian apolipoprotein E that has R112, R136 and R158 or a mammalian apolipoprotein E that has C112, R136 and C158, or coding for an antibody that binds to APOE4 or disrupts the binding of APOE to heparan sulfate proteoglycans.SELECTED DRAWING: None

The invention discloses an ovary-targeting mRNA liposome nanoparticle, a preparation method, a drug compound, a targeting delivery system and application, and relates to the technical field of liposome granules, the ovary-targeting mRNA liposome nanoparticle comprises the following components by mass: 20%-80% of SM-102, 1%-20% of PEG2000, 5%-40% of CHO-HP, 1%-20% of DSCP, and 0.01%-10% of targeting polypeptide, the target polypeptide comprises at least one of the following sequences: LVYKDPARPNTQK, RCGPCRLSSSDCGGPRTQPMACDLP, and CALCRRSTSDCGGPKDHPLT (recombinant human serum albumin), and the target polypeptide comprises at least one of the following sequences. The present invention provides a liposome nanoparticle for targeted ovary and uterus delivery of mRNA. The lipidosome nano-particles are specially researched, developed and designed for mRNA, have a good targeted delivery effect in mRNA in-vivo delivery, and can be applied to the field of targeted drug delivery of ovaries and uteruses. When in use, the kit can be directly prepared with a specific mRNA sequence for use, so that different application requirements can be flexibly met.

A system to determine therapeutic infusion volumes of a therapeutic infusate to administer to a target putamen of a subject to achieve a desired percent coverage of the therapeutic infusate within the target putamen. The system includes an input interface, a storage device, a processor, and output interface. The input interface receives data on a target putaminal volume of the target putamen, a number of target segmental regions of the target putamen, and the desired percent coverage. The storage device includes sample putaminal volumes, sample therapeutic infusion volumes, sample volumes of distribution, and a sample percent coverage. The processor determines the total therapeutic infusion volume of the therapeutic infusate to infuse into the target putamen. The output interface provides the total therapeutic infusion volume of the therapeutic infusate to achieve the desired percent coverage of the therapeutic infusate.

Adeno-associated virus (AAV) particles that are redirected with an antibody against CACNG1 and carry a nucleotide of therapeutic interest are provided. Also provided are methods of making and using the AAV particles, e.g., for treating a patient in need thereof or for manufacturing a medicament for treating a patient in need thereof.

The invention relates to pharmaceutical compositions comprising an iRNA agent, e.g., double stranded ribonucleic acid (dsRNA) agent and methods of using such compositions to treat a bleeding event in a subject having a hemophilia (e.g., with or without inhibitors).

The disclosure provides compositions and methods for the preparation, manufacture and use of an adeno-associated virus (AAV) particle for the vectorized delivery of an antibody molecule that binds to HER2.

Provided herein are novel AAV capsids and rAAV comprising the same. In one embodiment, vectors employing a novel AAV capsid show increased transduction of a selected target tissue as compared to a prior art AAV.

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 invention belongs to the technical field of biological medicines, and particularly relates to a recombinant oncolytic herpesvirus and application thereof. In order to solve the problems of insufficient replication efficiency, limited immune activation and the like of the existing oncolytic herpesvirus, the invention provides a recombinant oncolytic herpesvirus which contains a coding neurotoxic factor regulated by a tumor specific promoter or a gene related to replication and a gene segment for coding an immunomodulatory factor. Experiments prove that the recombinant oncolytic herpesvirus prepared by the invention has multiple advantages of high replication efficiency, strong tumor targeting, remarkable treatment effect on various tumors, high safety and the like, provides a brand new drug development thought and treatment choice for the field of tumor immunotherapy, and has important clinical application value and market prospect.

Provided herein are methods of expressing syntaxin-binding protein 1 (STXBP1) in a neuron. Also provided herein is a modified adeno-associated virus (AAV) encoding a STXBP1 under the control of a promoter operable in a brain cell or neuronal cell.

The present invention provides novel gene therapy compositions for use in treatment of Duchenne Muscular Dystrophy (DMD).

The present disclosure relates to compositions and methods for the treatment of cardiomyopathy. Several embodiments provided for herein relate to virally-mediated transfer of a gene to host cells to induce expression of an encoded polypeptide, protein or other product in order to ameliorate one or more symptoms of the cardiomyopathy in a subject. In several embodiments, the disclosed methods and compositions relate to recombinant adeno-associated virus particles encoding human TMEM43 in order to treat Arrhythmogenic cardiomyopathy.

Disclosed herein are nucleic acid compositions and methods of use. The nucleic acid compositions may have a therapeutic nucleic acid sequence operably linked to a nuclear targeting sequence that increases expression of the therapeutic nucleic acid in a cell by at least 1.25 fold; at least 80% sequence identity to SEQ ID NO: 6; or a first regulatory element comprising a promoter sequence operably linked to a hemoglobin subunit gamma intron (hBGi) sequence, and a second regulatory element comprising a woodchuck hepatitis posttranscriptional regulatory element (WPRE) sequence. The nucleic acid compositions with these features may enhance therapeutic nucleic acid transfection and expression. Also disclosed herein are transgenes optimized for gene therapy applications, including novel FVIII transgene sequences, in which the B domain may be non-naturally occurring the A1 and / or A3 domain may include at least one amino acid substitution.