32 results about "Gene Therapy Agent" patented technology

Methods and systems for monitoring and / or controlling production units used at various stages of biological product development and manufacturing are presented herein. In particular, in certain embodiments, the biological production monitoring and control techniques described herein utilize a mid-infrared (mid-IR) analyzer that is capable of obtaining mid-infrared spectral data from an aqueous sample in substantially real time. The techniques described herein can utilize this mid-infrared spectroscopic data to measure sample quality metrics, such as protein content, titer, secondary structure, aggregation, and the like, as well as viral and / or nucleic acid characteristics. Thus, sample quality metrics can be measured substantially in real time and / or continuously to assess, for example, the production quality of protein and gene therapeutic agents, and can be used by a control system to adjust and / or control process parameters to improve product quality, etc.

The disclosure relates to methods of delivering a gene therapy agent to a subject, treating an individual in need of a gene therapy agent, increasing expression of a gene therapy agent, reducing an immune response to a gene therapy agent, and preventing immune-related adverse events in a subject by administering a gene therapy agent and an IL-2 conjugate to the subject. The IL-2 conjugate has at least one amino acid residue replaced by an unnatural amino acid linked to a conjugating moiety. The disclosure further relates to methods of selecting a subject for treatment with a gene therapy agent and an IL-2 conjugate.

The present invention relates to gene therapy agents for the treatment of pulmonary alveolar proteinosis (PAP), particularly autoimmune PAP (aPAP). In particular, the present invention relates to gene therapy vectors which drive transient and / or low-level expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), which provide a therapeutic effect without therapy-associated toxicity. The invention further relates to related products and an animal model of aPAP.

The present invention relates to a base correction system that corrects mitochondrial DNA mutations G3460A, G11778A, or T14484C, which are present in patients with Leber's hereditary optic neuropathy (LHON), to a normal genotype. Specifically, the present invention provides a base editor capable of correcting a mutation site in a mitochondrial gene of an LHON patient to a normal genotype. The present invention also provides a method for correcting a mitochondrial gene mutation using a fusion protein or a polynucleotide encoding such a fusion protein that recognizes a specific site in the mitochondrial gene of an LHON patient and specifically corrects the adenine base at position 3460, the adenine base at position 11778, or the cytosine base at position 14484. The base editor or polynucleotide according to the present invention can be used in cells or in an extracellular test tube environment to correct DNA mutations specifically expressed in LHON, and more preferably, can be used as a gene therapy agent to prevent or treat the disease. Thus, the present invention also provides a use of the substance for preventing or treating Leber's hereditary optic neuropathy.

The present invention provides a novel gene-therapeutic agent for neurodegenerative diseases. The present invention allows AB variants to be secreted out of cells to allow wt AB polymerization to be slowed or inhibited and cytotoxicity to be reduced in the human body, and thus exhibits excellent effects of preventing, alleviating, and treating neurodegenerative diseases.

The present invention relates to a novel ionized lipid and a lipid nanoparticle composition using the same. The lipid nanoparticles comprising the novel ionized lipid according to the present invention exhibit excellent gene encapsulation rate and in vivo gene delivery rate, and as well as excellent gene delivery ability even upon re-administered, and thus can be advantageously utilized in the development of gene therapeutic agents for various indications.

The invention discloses a pH and enzyme dual-response type targeted DNA nano-carrier for relieving tumor cell hypoxia as well as a preparation method and application of the pH and enzyme dual-response type targeted DNA nano-carrier. The DNA nano-carrier comprises m tandem repeat units, each tandem repeat unit comprises a long single-stranded DNA repeat unit, three complementary short single-stranded DNAs and siRNA, each of the three complementary short single-stranded DNA sequences comprises a functional region and a base complementary region, and the functional region is a pH-responsive nucleic acid complementary sequence or a nucleic acid aptamer sequence for specifically targeting cancer cells; siRNA is a gene therapeutic agent for relieving tumor hypoxia, an extended positive-sense strand of siRNA comprises a 5 '-terminal extended pH response sequence and a positive-sense strand, and the 5'-terminal extended pH response sequence is complementary with a pH-responsive nucleic acid complementary sequence of the complementary short single-stranded DNA. The nano-drug carrier has excellent drug loading capacity and targeting property, can deliver anti-cancer drugs such as siRNA in a targeted manner, responds to a slightly acidic / enzyme environment of tumor cells and is quickly released, and the anti-tumor treatment effect is improved.

The present invention relates to a gene delivery platform for multi-organ sequential targeting oral administration, and to a gene delivery platform having a layer-by-layer chylomicron-mimicking self-assembly (lbl-CMSA), which is a lipid nanoparticle having a double-layer structure. A gene delivery platform for oral administration according to the present invention allows a second layer containing the outermost bile acid to exhibit high durability in the gastrointestinal tract even under various pH and enzyme actions, allows a gene drug encapsulated by an intestinal active target mechanism of bile acid to be primarily delivered to intestinal cells, and allows a first layer containing apolipoprotein to be delivered to lymphatic vessels through a chylomicron-mimicking pathway, thereby allowing the gene drug encapsulated therein to secondarily reach a target organ via a circulatory pathway in the body. Therefore, the gene delivery platform for oral administration of the present invention can be used as an effective oral administration formulation having increased bioavailability by loading, on the platform, a combination of gene therapeutic agents sequentially targeting the intestine and various organs.

The present invention relates to: an antisense oligonucleotide (ASO) targeting an FKS1 gene, an FKS2 gene, a CHS3 gene and / or a GWT1 gene of a Candida sp. fungus; an antibacterial composition comprising same; and a pharmaceutical composition for preventing or treating diseases caused by pathogenic fungi. The ASO according to the present invention can be used as a gene therapeutic agent having a fungus-specific antibacterial effect by specifically inhibiting FKS1, FKS2, CHS3 and / or GWT1 genes, and can be a useful gene therapeutic agent that can be used in combination with or replace conventional antifungal agents for antifungal agent-resistant fungi or multidrug-resistant fungi.

The present disclosure relates to a method of detecting an integration site of a vector in a genome. According to the method of the present disclosure, it is possible to simply and quickly analyze a quantitative integration site of a viral vector with respect to a plurality of DNA motifs (sites) in a genome. Therefore, it can be useful for monitoring the safety and effectiveness of a gene therapy agent.

The present disclosure relates to an adeno-associated virus vector capable of smooth muscle cell-specific gene delivery. With significantly enhanced tropism for smooth muscle cells, the adeno-associated virus variants of the present disclosure can be advantageously applied as a gene therapeutic agent for treating smooth muscle-related diseases.

The present invention relates to polymer-based nucleic acid molecule (e.g., mRNA) transporters having ionizable moieties. More specifically, the present invention provides novel polymers that can transport any negatively charged dielectric substance to a desired site, depending on the length of the monomer and polymer. The polymers of the present invention can be effectively used in gene therapy agents or vaccines containing genetic material, such as mRNA, for therapeutic or prophylactic purposes.

The present disclosure relates to a dual helper plasmid for producing a recombinant adeno-associated virus. A double transfection method using the dual helper plasmid of the present disclosure is advantageous over the triple transfection method typically used for production of adeno-associated virus in terms of 1) increased chance of co-transfection, 2) increased productivity of recombinant adeno-associated virus, 3) reduction in cost and time of plasmid production and purification, etc., and thus can be usefully utilized for effective production of a gene therapy agent.

The present invention provides gene or RNA therapeutic vectors for use in the treatment of non-malignant CNS disorders, which are to be injected into the pons by convection-enhanced delivery (CED). The invention also provides a method for treating non-malignant CNS disorders, comprising injecting a gene or RNA therapeutic vector into the pons of a subject in need (CED), and a method for distributing a gene therapy agent throughout the nervous system, wherein a viral vector transported anterograde and retrogradely is injected into the pons and middle cerebellar peduncle of a subject from a cannula inserted from the cerebellum and middle cerebellar peduncle into the pons.

The invention provides an oligonucleotide hydrogel micro-nano gene compound as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The preparation method comprises the following steps: firstly, designing C5ASO, and loading the C5ASO on a nano-carrier modified with HAP-1 peptide (targeting fibroblast-like synovial cells) and active ester; meanwhile, the porous HAMA hydrogel microspheres are prepared by utilizing a photo-crosslinking micro-fluidic technology; then, DBCO-TIMP and an azide group are respectively introduced into the liposome and the hydrogel microspheres through Michael addition and an amide coupling reaction, so that a micro-nano gene compound (C5ASO (at) HAP-CL-TIMP (at) HMs) is formed; in addition, the liposome and the hydrogel microspheres are efficiently compounded through click chemistry. The hydrogel micro-nano gene compound not only can efficiently load ASO lipidosome, but also can enhance the stability of a gene therapeutic agent in an in-vivo delivery process. Meanwhile, the MMP-9 response peptide structure in the RA articular cavity inflammation microenvironment can be accurately activated, so that continuous complement intervention is realized.

The present invention relates to a gene therapy method capable of continuously and efficiently correcting genes, and a gene therapy product using same. It is expected that the gene therapy product of the present invention can present clues for gene therapy for muscular diseases including Duchenne muscular dystrophy.

The present invention relates to a base editing system that edits G3460A, G11778A, or T14484C, which is one of mitochondrial DNA mutations in a patient with Leibler hereditary optic neuropathy (LHON), to a normal genotype. Specifically, provided is a method for editing a mitochondrial gene mutation using a fusion protein or a polynucleotide encoding such a fusion protein as a base editor capable of editing a mutation site of a mitochondrial gene of an LHON patient to a normal genotype, the specific site of the mitochondrial gene of the LHON patient can be recognized, and the activity of the 3460 or 11778 adenine base or 14484 cytosine base is specifically edited. By using the base editor or the nucleotide according to the present invention, it is possible to edit DNA mutations specifically occurring in LHON in a cell or extracellular test tube environment, and more preferably, it is possible to be used as a gene therapeutic agent for preventing or treating the disease. Thus, the present invention also provides the use of said substance for the prevention or treatment of lebsiella hereditary optic neuropathy.

Compositions and methods of use characterized by nucleic acids and vectors. In particular, the present disclosure features nucleic acid compositions and methods relating to temporally modulating expression of gene therapeutics comprising a therapeutic transgene. The disclosed compositions, methods, and uses relate to gene and cell therapy.

The present invention relates to a nucleic acid molecule (e.g., mRNA) delivery carrier based on a polymer having an ionized moiety. Specifically, the invention provides a novel polymer which can deliver all negatively charged genetic materials to a target site according to the length of monomers and polymers. The polymer according to the present invention can be effectively used in a gene therapeutic agent, a vaccine or the like containing a genetic material for therapeutic or prophylactic purposes, such as mRNA.

This disclosure provides methods of profiling gene therapy agents, comprising administering a library comprising one or more gene therapy agents to a non-human subject or an ex vivo or in vitro cell population, wherein the one or more gene therapy agents each comprise an identifying sequence, wherein the identifying sequence is operably linked to an RNA polymerase III promoter and / or the identifying sequence is operably linked to a capture sequence.

The present invention relates to gene therapeutics for the treatment of alveolar proteinosis (PAP), in particular autoimmune PAP (aPAP). In particular, the present invention relates to gene therapy vectors that drive transient and / or low levels of expression of granulocyte-macrophage colony stimulating factor (GM-CSF) that provide therapeutic effects without the presence of toxicity associated with treatment. The invention also relates to related products and animal models of aPAP.

Featured are compositions and methods of use in conjunction with gene therapy agents. In particular, the disclosure features compositions and methods designed to permanently and / or site- specifically alter expression of a gene therapy agent comprising a therapeutic transgene.

The present invention relates to a gene therapy method capable of continuously and efficiently correcting genes, and a gene therapeutic agent using same. The gene therapeutic agent of the present invention is expected to be able to treat genetic diseases including Duchenne muscular dystrophy and cystic fibrosis, and furthermore, to provide therapeutic cues for a wide range of diseases caused by genetic defects.

The present invention relates to a method for producing extracellular vesicles into which a therapeutic gene is introduced by electroporation, a wound-healing pharmaceutical composition produced by the method, and a wound-healing pharmaceutical preparation or quasi-drug preparation comprising same as an active ingredient. The extracellular vesicles derived from mesenchymal stem cells (MSCs), fibroblasts, and colostrum, produced by the present method, are all non-cytotoxic, have excellent nucleic acid delivery efficiency, and thus allow for stable expression. In particular, by introducing a vascular endothelial growth factor (VEGF) gene, which is known to have a wound-healing effect, into extracellular vesicles derived from mesenchymal stem cells (MSCs), fibroblasts, and colostrum through electroporation, VEGF gene-introduced extracellular vesicles produced by the production method of the present invention can be used as a gene therapy agent for wound healing.

The present invention relates to a method for enhancing gene therapy by using effective enzymes to degrade or digest serum antibodies and / or inhibit or reduce the effector function of serum antibodies in a subject. More specifically, the subject either has no detectable antibodies that specifically bind to the gene therapy agent, or has a low titer of neutralizing antibodies (NAbs) that specifically bind to the gene therapy agent, or a low titer of total antibodies (TAbs) that specifically bind to the gene therapy agent. The method extends the serum half-life of the therapeutic agent, meaning that the gene therapy agent can be administered at a lower dose than would otherwise be administered.

The present invention relates to gene therapy agents for the treatment of pulmonary alveolar proteinosis (PAP), particularly autoimmune PAP (aPAP). Specifically, the present invention relates to gene therapy vectors that drive transient and / or low-level expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), resulting in a therapeutic effect without the toxicity associated with the therapy. The present invention further relates to related products and animal models of aPAP.

The present disclosure relates to a dual helper plasmid for producing a recombinant adeno-associated virus. A double transfection method using the dual helper plasmid of the present disclosure is advantageous over the triple transfection method typically used for production of adeno-associated virus in terms of 1) increased chance of co-transfection, 2) increased productivity of recombinant adeno-associated virus, 3) reduction in cost and time of plasmid production and purification, etc., and thus can be usefully utilized for effective production of a gene therapy agent.

Provided herein are methods of enhancing gene therapy in an individual by administering an IRAK degrading agent in conjunction with the gene therapy to suppress natural immunity to the gene therapy. In some embodiments, the gene therapy uses an adeno-associated virus (AAV) vector, an adenovirus vector, a lentivirus vector, a herpes simplex virus (HSV) vector, or a lipid nanoparticle. Also provided herein are methods of selecting an individual for treatment with an IRAK degrading agent in combination with a gene therapy agent.

The present invention relates to multi-layer nanoparticles for nucleic acid delivery, a method for preparing same, a nucleic acid delivery composition comprising same, an antibacterial composition, and a pharmaceutical composition for preventing or treating infectious diseases. The multi-layer nanoparticles for nucleic acid delivery comprise: gold nanoparticles; a polyethyleneimine modified on the surface of the gold nanoparticles; and chitosan applied on the gold nanoparticles modified with the polyethyleneimine. According to the present invention, the introduction of nucleic acids (e.g., ASOs) into target bacterial cells is maximized, and highly efficiently loaded nucleic acids can be effectively delivered into bacteria to maximize the effect of inhibiting target nucleic acids, and thus the present invention can be useful as an antibacterial agent and a gene therapeutic agent.

Provided herein is a method for determining the natural immunogenicity of a gene therapy agent in an individual. Specifically, the method involves the use of isolated dendritic cells to detect the natural immunogenicity to a gene therapy agent. Exemplary gene therapy agents include adeno-associated virus (AAV) vectors, adenovirus vectors, lentivirus vectors, herpes simplex virus (HSV) vectors, or lipid nanoparticles.