489 results about "Genetic therapy" patented technology

A federated distributed computational system enables secure oncological therapy optimization through robotic integration. The system establishes a distributed graph architecture with secure communication channels connecting computational nodes, implementing encryption protocols for cross-institutional data exchange. Each node contains processing capabilities for fluorescence-guided imaging, uncertainty quantification, and expert knowledge integration while maintaining hierarchical knowledge graphs of oncological biomarkers, interventions, and outcomes. The system coordinates domain-specific knowledge through token-space communication and implements an advanced robotic integration system for surgical interventions using spatiotemporal tumor mapping, multi-modal fluorescence imaging, surgical robot coordination, and space-time stabilized mesh management. Key capabilities include wavelength-specific multi-modal fluorescence detection, combined epistemic and aleatoric uncertainty estimation, tensor-based data integration with adaptive dimensionality control, and light cone search for adaptive treatment optimization—all while maintaining strict privacy controls.

A three-dimensional scaffold for use in engineered tissue includes a repeated 3D geometry; and at least one of a hydrogel, a biocompatible polymer, and a bioprintable polymer. The repeated 3D geometry may include an open geometry including a plurality of interconnected nodes configured to be seeded with living cells. The scaffold may be formed via bioprinting. The three-dimensional scaffold may also be used for (1) 3D tissue modelling (for liver, kidney, gut, pancreas, heart, lung, spleen, etc.), (2) disease modeling of different tumor types such as breast, colorectal, lung, liver, brain, ovarian and others, (3) drug testing / therapeutic screening of small molecule drugs, peptides, proteins, antibodies, ADCs, gene therapies, RNA-based therapeutics, cell therapies, and tissue therapies, and (4) therapeutic / drug delivery (i.e., via delivery device that can be used to control drug release based on different patterns).

The invention discloses an acid responsive nanoprobe as well as preparation and anti-tumor application thereof. The nanoprobe has a core-shell structure, takes a nanoparticle self-assembled by a polycation aggregation-induced emission (AIE) photosensitizer and functional nucleic acid as a core, and takes a hyaluronic acid modified metal polyphenol network as a shell. The nanoprobe utilizes the acid responsiveness and broad-spectrum absorption performance of the metal polyphenol network and the diagnosis and treatment advantages of the polycation AIE photosensitizer to realize the acid responsiveness'switch 'controllable diagnosis and treatment of the tumor nanoprobe. In a neutral environment, the fluorescence is weak, the generation of ROS is less, and the background noise signal of the nanoprobe and the toxicity of non-targeted tissues are reduced; in an acid environment, fluorescence is enhanced, the ROS yield is improved, and the treatment efficiency and the curative effect monitoring accuracy are improved. The nano diagnosis and treatment probe is ingenious in design and simple to prepare, and can realize PDT and gene therapy synergistic anti-tumor, in-situ real-time report of early tumor treatment effect and assistance in precise cancer treatment.

Disclosed are AAV viral-based vector compositions useful in delivering a variety of nucleic acid segments, including those encoding therapeutic polypeptides to selected mammalian host cells for use in therapeutic autoimmune modalities, including, for example, the in vivo induction of immunological tolerance via a liver-directed AAV-based gene therapeutic regimen for treating and / or ameliorating autoimmune disorders such as multiple sclerosis. Further disclosed are nucleic acid segments encoding therapeutic polypeptides that have been codon-optimized for expression in human cells.

Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5' inverted terminal repeat (ITR), an expression cassette comprising engineered nucleic acid sequence encoding human Tafazzin and operably linked thereto regulatory sequences, and an AAV 3' ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treatment of Barth Syndrome or a disease associated with a mutation in a Tafazzin (TAZ) gene.

The present subject matter relates to recombinant lentiviral transfer plasmids for producing lentiviral vectors with increased vector titer and performance. These transfer plasmids are constructed so that a central polypurine tract (cPPT) is centered between the lentiviral LTRs and include a 6x stop codon sequence block downstream of the 3' LTR. When the transfer plasmids comprise a globin expression cassette, the lentiviral vectors produced therefrom are useful for treating hemoglobinopathies by gene therapy. Transduced cells, pharmaceutical compositions and methods of treating or ameliorating hemoglobinopathies with these lentiviral vectors are also provided. Additional transfer plasmids, cells, and compositions are provided that are useful for delivering any gene of interest to a cell, as well as plasmids for production of lentiviral vectors for treating other erythroid-specific diseases or disorders such as anemia and cancer.

The invention belongs to the field of gene therapy, and relates to a DNA (deoxyribonucleic acid) molecule for targeted degradation of target protein and application. The DNA molecule comprises at least one group of D-PROTAC units, each group of D-PROTAC units comprises at least one first DNA chain segment for coding a ubiquitin ligase targeting peptide and at least one second DNA chain segment for coding a target protein targeting peptide, and a third DNA chain segment for coding a connecting peptide is optionally arranged between the adjacent first DNA chain segment and second DNA chain segment. The gene therapy specific PROTAC molecular model is successfully constructed, the huge potential of a gene therapy method in the aspects of research, development and application of new PROTAC anticancer drugs is proved, the action mode of the PROTAC technology is innovated, and a new treatment application scene is expanded for gene therapy.

The present disclosure relates to a truncated ATP7B in which CRE5 and / or CRE6 is present, optionally CRE1 and / or CRE2 is present. The present disclosure also provides an adeno-associated viral vector encoding the truncated ATP7B for use in gene therapy for the treatment of Wilson's disease (WD).

The invention relates to guide polynucleotides and methods for targeting and editing a portion of the 5' UTR-encoding region of genes encoding VGSC alpha subunits (NaV) to abrogate or create an upstream open reading frame (uORF). The invention relates to guide polynucleotides and methods for targeting and editing a portion of the 5' splice acceptor site (SA) of an exon of a gene encoding a voltage-gated sodium channel (VGSC) alpha subunit (NaV). The invention also relates to use of the guide polynucleotides and methods for treating genetic disorders, in particular Dravet syndrome.

The invention belongs to the technical field of gene editing, and discloses a construction method of a uterus specific conditional gene editing mouse based on a CRISPR-AsCas12a system. According to the invention, the efficient editing ability of AsCas12a is innovatively combined with the uterus tissue specific Pgr promoter. According to the invention, rapid and efficient single gene knockout, such as Ythdf1, Ythdf2 and Ythdf3, is realized in the uterus. The technology breaks through the limitation of long breeding period of the traditional Cre / loxP system, and tissue-specific knockout can be realized without homozygosis. The CRISPR / AsCas12a system provides an animal model for researching pregnancy-related diseases and hormone regulation mechanisms and developing a uterus targeted gene therapy. Reference is provided for exploring other gene editing model animals, and development of gene editing animal models in the veterinary field is broadened.

Disclosed herein are embodiments of a polymer-based implant and methods of making and using the same. The polymer-based implant comprises a polymer component and a therapeutic agent. In some embodiments, the polymer-based implant can be used to treat and / or prevent retinal diseases and / or retinopathies. The polymer-based implant exhibits physical properties that provide the ability to safely place the polymer-based implant in an ocular region without undesired diffusion and also to allow for controlled and timely release of the therapeutic agent to a desired region of the ocular region, such as the retina. In particular disclosed embodiments, the polymer-based implant can be used for safe and effective gene therapy.

Featured are the use of pharmaceutical compositions containing a CD40 antagonist or a CD154 antagonist for the treatment, reduction, and / or inhibition of an immune response, such as an anti-drug antibody response, following, e.g., protein replacement therapy or gene therapy.

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 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.

This present disclosure provides adeno-associated viral vectors, recombinant adeno-associated virus (rAAV), and methods of their use in gene therapy for treating propionic acidemia (PA). Also provided are pharmaceutical compositions comprising a recombinant adeno-associated virus of the invention and a pharmaceutically acceptable carrier or excipient. These pharmaceutical compositions may be useful in gene therapy for the treatment of PA caused by mutations in propionyl-CoA carboxylase α-subunit (PCCA) or mutations in propionyl-CoA carboxylase β-subunit (PCCB).

This present disclosure provides adeno-associated viral vectors, recombinant adeno-associated virus (rAAV), and methods of their use in gene therapy for treating propionic acidemia (PA). Also provided are pharmaceutical compositions comprising a recombinant adeno-associated virus of the invention and a pharmaceutically acceptable carrier or excipient. These pharmaceutical (compositions may be useful in gene therapy for the treatment of PA caused by mutations in propionyl-CoA carboxylase α-subunit (PCCA) or mutations in propionyl-CoA carboxylase β-subunit (PCCB).

The invention relates to gene therapy of ocular conditions. Described herein are compositions and methods for delivering therapeutic products, such as therapeutic proteins (e.g., antibodies), therapeutic RNAs (e.g., shRNAs, siRNAs, and miRNAs), and therapeutic aptamers, to the retinal / vitreous humor of the eye of a human subject to treat ocular conditions, involving, for example, recombinant viral vectors, such as recombinant adeno-associated virus (rAAV) vectors.

Provided herein is a nucleic acid encoding a prion protein, wherein the prion protein (a) comprises an amino acid sequence comprising a protective sequence variant such as a G127V mutation and (b) lacks a fully functional 3' glycosylphosphatidylinositol (GPI)-anchor attachment sequence. Also provided are viral vectors and pharmaceutical compositions comprising the nucleic acids. Further provided are methods and uses of treating prion diseases or other neurodegenerative diseases that confer toxicity through cell surface- anchored prion proteins in a subject, comprising administering to the subject an effective amount of a pharmaceutical composition or viral vector described herein.

Provided herein are codon-optimized Smad7 polynucleotides and vectors comprising codon-optimized Smad7 polynucleotides for use in increasing or prolonging Smad7 expression in a subject.

What is described is a peptide for use in the reduction of side-effects in form of immunostimulatory reactions / effects which occur with gene therapy, wherein the peptide is coupled to a nucleic acid molecule used in gene therapy. Furthermore, such a peptide is described for use in the reduction of side-effects in form of immunostimulatory reactions / effects which occur with gene therapy, wherein the peptide is coupled to a nucleic acid molecule used in gene therapy, wherein the immunostimulatory reactions / effects are induced by activation of IFIT1 / 2, IRF9, TLR3, TLR7, TLR8 or PKR.

A composition including a gene therapy delivery system and an alpha-galactosidase (GLA) polynucleotide encoding a GLA polypeptide, wherein the GLA polypeptide has at least 95% sequence identity to one of SEQ ID NOS. 1-40, 44-45, 51-52, 57, 61-173 or 212. Also provided are compositions, formulations, fusion proteins, and methods for the treatment of Fabry disease.

The invention belongs to the field of pathologies affecting the central nervous system: in particular, severe cerebral pathologies, more particularly those restricted by the presence of the blood-brain barrier (BBB): gliomas, cerebral metastases, neurodegenerative diseases (e.g. Alzheimer's, Parkinson's or ALS), genetic diseases (Huntington's, myopathies, Leigh syndrome, Rett syndrome), but also to the field of cancers, musculoskeletal and immunological disorders, vascular diseases (thrombus) in numerous organs (e.g. liver, kidney or muscle) and in combination with numerous therapeutic approaches (e.g. chemotherapy, immunotherapy, targeted therapy or gene therapy). The invention relates to a microbubble comprising a fluorinated polymer or copolymer and a fluorinated gas, to the use thereof and also to the polymer or copolymer intermediate compounds.

The present invention relates to the prevention or mitigation of adverse reactions associated with gene therapy, such as the formation of anti-drug antibodies. In particular, the present invention relates to the use of tyrosine kinase inhibitors, such as dasatinib, to prevent or ameliorate such side effects.

Provided herein are polynucleotides comprising a coding sequence for expression of a fibroblast growth factor 21 (FGF21) pathway activating agent. Also provided are vectors, recombinant viral genomes, and recombinant virus compositions comprising said polynucleotides, as well as associated methods.

Variants of coagulation factor VIII (FVIII) and expression cassettes encoding the FVIII variants thereof are described. A variant FVIII includes a glycoepitope of the FVIII protein including an N2118Q mutation. The N2118Q mutation can be combined with other mutations including a BDD-FVIII, N6, V3, RH, furin-cleavage site deletion. X10, K12, and / or F309S mutation to form additional FVIII variants. The FVIII variants with the N2118Q mutation and expression cassettes thereof can result in reduced immunogenicity of the resulting protein. When combined with other FVIII mutations, higher gene expression, increased secretion, increased stability, and higher FVIII functional activity can be achieved by the expressed FVIII variants. The variant FVIII and expression cassettes described here can be useful in protein replacement therapy and / or gene therapy for the treatment of hemophilia A.

The present invention relates to the delivery of CLN6 polynucleotides by adeno-associated viruses. The present disclosure relates to the delivery of a recombinant adeno-associated virus (rAAV) to a neuronal wax lipofuscia neuron 6 (CLN6) polynucleotide. The present disclosure provides rAAVs and methods of using the rAAVs for CLN6 gene therapy of neuronal wax-like lipofuscin deposition disease or CLN6 type Brattan disease.

The present invention provides an agent for protecting and regenerating pancreatic beta cells in a mammal having diabetes, the agent containing a recombinant viral vector that expresses hepatocyte growth factor (HGF), wherein the agent is characterized by being administered in a dose of 1010-1012 virus particles (vp) / kg body weight, and by the virus vector including a nucleic acid that encodes HGF downstream of a promoter having transcription activity capable of yielding a therapeutically effective HGF level in the blood at said dose.

Aspects of the disclosure relate to compositions and methods useful for delivering minigenes to a subject. Accordingly, the disclosure is based, in part, on isolated nucleic acids and gene therapy vectors, such as viral (e.g., rAAV) vectors, comprising one or more gene fragments encoding a therapeutic gene product, such as a protein or peptide (e.g. a minigene). In some embodiments, the disclosure relates to gene therapy vectors encoding a USH1B protein (e.g. the gene product of USH1B, also referred to as MY07A) or a portion thereof. In some embodiments, compositions described by the disclosure are useful for treating diseases associated with mutations in the USH1B (MY07A) gene, for example Usher Syndrome.

The present invention provides novel conjugates comprising a magnetic particle and a multitude of viral structures covalently bound to said particle. These conjugates are suited for efficient extracorporeal removal of antibodies from blood. In particular, the conjugates are suited as adjuvant treatment in gene therapy.

The present invention provides gene therapies for the treatment of Friedreich's ataxia. Specifically, the present invention provides a nucleic acid, cloning vector and transfer vector for the production of an adeno-associated virus (AAV) vector. The nucleic acid comprises (i) a nucleic acid sequence encoding frataxin, (ii) a phospho-glycerate-kinase (PGK) promoter, and (iii) a woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). The present invention also provides a pharmaceutical composition which comprises the AAV vector or nucleic acid. Also, the AAV vector, nucleic acid or pharmaceutical composition can be used as a medicament, specifically as a medicament for the treatment of Friedreich's ataxia.