234results about "Genetic material administration regime" patented technology

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.

Provided herein is a method for improving delivery of a pharmaceutical composition to the central nervous system in a subject in need thereof, the method comprising administering to the subject, in combination with the pharmaceutical composition, an agent that enhances glymphatic influx.

To provide compositions and methods for regulating protein production in target cells. [Solution] The compositions and methods disclosed herein can improve diseases associated with protein or enzyme deficiency. The present invention provides, for example, a composition comprising (a) at least one mRNA molecule that is at least partly encoding a functionally secreted polypeptide, and (b) a transport vehicle comprising lipid nanoparticles. The present invention also provides a method for treating a subject deficient in a functional polypeptide, comprising administering a composition comprising (a) at least one mRNA that is at least partly encoding the functionally secreted polypeptide, and (b) a transport vehicle comprising lipid nanoparticles, wherein after administration of the composition, the mRNA is expressed in a target cell to produce the functionally secreted polypeptide.

Nanoparticles comprising a nucleic acid molecule encoding human ubiquitin-like protein 5 (UBL5) or human UBL5 protein are provided. Methods of treating a disease, disorder or condition characterized by mitochondrial stress are provided. Expression vectors, nucleic acid molecules, peptides, pharmaceutical compositions and methods of identifying a gene for use in gene therapy, targeting an agent to a CD44 expressing cell and producing a therapeutic nanoparticle are also provided.

Provided herein is a gene therapy for JPH2 (junctophilin-2), for example, using an adeno-associated virus (AAV) vector. The promoter of the vector can be the MHCK7 promoter or the cardiac troponin T (HTNNT2) promoter. The capsid can be the AAV9 or AAVrh74 capsid or a functional variant thereof. Other promoters or capsids may be used. Further provided are methods of treatment, such as by intravenous, intracoronary, intracarotid or intracardiac administration of rAAV vectors, as well as other compositions and methods. TIFF2024546103000093.tif151154

Provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of at least one CD122 / CD132 agonist, at least one immune checkpoint inhibitor and a viral composition comprising one or more viruses engineered to overexpress a tumor suppressor gene and / or an adenoviral death protein. Also provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of at least one oncolytic viral composition and at least one CD122 / CD132 agonist and at least one immune checkpoint inhibitor. Also provided herein are methods of enhancing anti-tumor efficacy by administering the agents described above in combination with other cancer therapies. In highly aggressive forms of cancer, known to be generally resistant to immune therapies, these treatments unexpectedly resulted in complete tumor remissions and curative outcomes.

AAV vectors are ideally suited for long-term delivery of a combination of broadly neutralizing antibodies to achieve sterilizing immunity to HIV. Unfortunately, host immune responses to the delivered antibody have severely limited the efficacy. The TLR9 pathway has been identified in initiating adaptive immune responses against AAV and delivered bNAbs. To enhance this strategy, we validated Hydroxychloroquine, a known drug inhibitor of the TLR9 pathway, as a pretreatment to AAV delivery to avoid anti-drug antibody responses. TLR9 signaling inhibition was validated using a HEK-Blue hTLR9 reporter cell line and CpG stimulation. Hydroxychloroquine was also validated in a 3-macaque trial where AAV9-3BNC117 and AAV9-10-1074 were administered along with 3 doses of hydroxychloroquine once a week starting 1 week before AAV inoculation. Unlike historical controls, where 3BNC117 and 10-1074 expression is lost within the first 4-5 weeks, 2 macaques maintained 10-1074 expression and 1 macaque maintained 3BNC117 for the duration of the trial. Anti-3BNC117 antibodies were only observed in 2 of the 3 macaques and were significantly delayed. Anti-10-1074 antibody responses were a log lower than typically observed in historic controls. The use of hydroxychloroquine as a pretreatment for AAV inoculation is a promising strategy. The significant decrease in anti-10-1074 antibody levels and the successful delivery of 10-1074 in 2 macaques and 3BNC117 in 1 macaque was very encouraging. Extending the dosage of hydroxychloroquine beyond 3 doses may be sufficient to observe long-term bNAb expression in all animals and further decrease ADA responses. Together, these data suggest that the short-term treatment of hydroxychloroquine at the time of AAV inoculation has a meaningful impact on tolerance induction to our AAV-delivered bNAbs.

The invention relates to a method or regimen comprising the administration of IgG cysteine protease to a subject in order to improve the benefit of a subsequent vector-based therapy, where the vector-based therapy treats a disease or condition in said subject. Accordingly, the invention also relates to the treatment of diseases or conditions with a vector-based therapy. The method comprises administering to the subject at least two doses of an IgG cysteine protease; and subsequently administering said vector-based therapy. Methods of the invention are particularly useful for subjects who have pre-existing immunity or pre-existing neutralizing antibodies against the vector-based therapy.

The present invention relates generally to the field of molecular biology. In particular, the specification teaches methods of preventing or treating an RNA viral infection in a subject.

Disclosed herein is a method for the treatment of Pompe disease, comprising administering a recombinant AAV (rAAV) vector comprising a rAAV genome comprising a heterologous nucleic acid encoding an acid alpha-glucosidase (GAA) polypeptide operably linked to a liver-specific promoter, wherein the subject has been discontinued or is not receiving enzyme replacement therapy (ERT).The technology described herein generally relates to gene therapy constructs, methods and compositions for the treatment of Pompe disease.

The present invention relates to methods for treating diseases by the in vivo gene editing of hematopoietic stem and progenitor cells (HSPCs), and in particular to the use of a CXCR4 antagonist to increase the efficiency of HSPC gene editing in vivo when administered prior to or in conjunction with administration of a gene editing system to a subject in need thereof.

The present disclosure relates to chimeric adeno-associated virus capsids and related adeno-associated viruses targeting glial progenitor cells.

Methods for treating a human suffering from osteoarthritis are provided. Aspects of the methods include intra-articularly administering to the human a dosage comprising a nucleic acid coding sequence for a human interleukin-1 receptor antagonist (IL-1Ra) in combination with a dosage of an immunomodulatory agent to treat the human suffering from osteoarthritis. Also provided are compositions for use in practicing the methods.

The present disclosure provides a composition comprising a recombinant adeno-associated virus (AAV) vector containing a heterologous nucleic acid, sodium chloride, potassium chloride, magnesium chloride, phosphate buffer, and a non-ionic surfactant at a pH of 7.2 to 7.4. The present disclosure further provides a method of treating a neurological disorder in a subject, the method comprising administering the composition directly to the central nervous system of a subject in need thereof.

Compositions and methods are described herein for treating subjects having hypercholesterolemia and / or cardiovascular disease.

In some embodiments, the present disclosure relates to nucleic acids, compositions and methods for delivering therapeutic genes to a subject. In some embodiments, the therapeutic genes are delivered via the use of viral vectors. In some embodiments, the viral vector is an adeno-associated virus. In some embodiments, the therapeutic genes are delivered to treat heart disease, injury or other disorders.

To provide a method of treating a disease caused by loss of function or activity of protein.SOLUTION: A method includes: (a) a step of removing, reducing, depleting, inhibiting, inactivating, or capturing an AAV binding antibody from a blood product obtained from the subject by a process including apheresis; and (b) a step of administering a certain amount of recombinant adeno-associated virus (rAAV) vector containing heterologous polynucleotide coding protein or peptide which provides or assists the function or activity of the protein.SELECTED DRAWING: None

This invention relates to nucleic acids that encode and express full-length rod-derived cone survival factor (RdCVF) and human IgK signaling sequences, as well as viral vectors containing these nucleic acids. The invention also relates to compositions and pharmaceutical preparations containing these nucleic acids or vectors, methods for producing or secreting full-length RdCVF and human IgK signaling sequences, and therapeutic methods.

Provided herein are systems, methods, and compositions for a Remote-Controlled Alteration / Induction of Cellular Apoptosis. In one embodiment, the method comprises radio- controlled mRNA therapy to treat cancer.

In several embodiments, the present disclosure relates to nucleic acids, compositions, and methods for the delivery of a therapeutic gene to a subject. In several embodiments, the therapeutic gene is through the use of a viral vector. In several embodiments, the viral vector is an adeno-associated virus. In several embodiments, the therapeutic gene is delivered to treat a cardiac disease, injury or other disorder.

The present invention relates to compositions and methods that can target B cells and / or hematopoietic stem cells (HSCs), manipulate these cells, and express specific antibodies ex vivo or in vivo to become part of the host's long-term immune repertoire.

The present disclosure relates to pharmaceutical compositions, kits, methods and uses thereof, that include a corticosteroid and an adenoviral-based delivery and expression system. In some embodiments, the compositions, kits, methods and uses thereof, improve one or more of transduction, expression, efficacy and / or safety of the adenoviral-based delivery and expression system when administered to an animal as compared to administration of the same pharmaceutical composition without the corticosteroid.

Disclosed herein are compositions comprising AAV9 viral vectors and methods of using the same to treat SMA patients, such as type II and type III spinal muscular atrophy (SMA) patients.

The present disclosure relates to pharmaceutical compositions, kits, methods and uses thereof comprising a corticosteroid and an adenovirus-based delivery and expression system. In some embodiments, administration of the compositions, kits, methods, and uses thereof to an animal may improve one or more of transduction, expression, efficacy, and / or safety of an adenovirus-based delivery and expression system as compared to administration of the same pharmaceutical composition without corticosteroids.

The present application is directed, in general, to tolerizing immune mediated particles comprising gene therapy vector antigens for use in combination with gene therapy regimens in order to reduce immunogenicity to the gene therapy vector antigens and / or transgene protein products expressed by the vectors.

The present invention relates to nucleic acids encoding and capable of expressing full-length rod-derived cone cell viability factor (RdCVF) and human IgK signal sequences and viral vectors containing these nucleic acids. The invention also relates to compositions and pharmaceutical formulations comprising these nucleic acids or vectors, methods of generating or secreting full-length RdCVF and human IgK signal sequences, and methods of treatment.

The present disclosure relates to pharmaceutical compositions, kits, methods and their uses, comprising a corticosteroid and an adenovirus-based delivery and expression system.In some embodiments, the compositions, kits, methods and their uses improve one or more of the transduction, expression, efficacy and / or safety of the adenovirus-based delivery and expression system when administered to an animal, compared with the administration of the same pharmaceutical composition without a corticosteroid.

Nucleic acid constructs and compositions that allow insertion of a multidomain therapeutic protein (e.g., GAA fusion protein) coding sequence into a target genomic locus such as an endogenous ALB locus and / or expression of the multidomain therapeutic protein (e.g., GAA fusion protein) coding sequence are also provided. The nucleic acid constructs and compositions can be used in methods of integration of a multidomain therapeutic protein (e.g., GAA fusion protein) nucleic acid into a target genomic locus, methods of expression of a multidomain therapeutic protein (e.g., GAA fusion protein) in a cell, methods of reducing glycogen accumulation, methods of treating Pompe disease or GAA deficiency in a subject, and method of preventing or reducing the onset of a sign or symptom of Pompe disease in a subject, including neonatal cells and subjects.

Compositions and methods are described for the delivery of a fully human post-translationally modified therapeutic monoclonal antibody, or an antigen binding fragment thereof, that binds to C3 or C5 to a human subject for treatment of an ocular indication, particularly AMD. Also provided are compositions and methods for the delivery hCHL1 to a human subject for treatment of an ocular indication, particularly AMD. The nucleotide sequence encoding the antibody is delivered in a rAAV vector that targets ocular tissue cells for expression of the transgene.