125results about "Genetic material delivery route" patented technology

The disclosure relates to compositions and methods for altering, e.g., enhancing, the level of frataxin protein via delivery using an adeno-associated viral (AAV) capsid variant. The compositions and methods of the present disclosure are useful in the treatment of subjects who have, have been diagnosed with having, or are at risk of having a disorder associated with frataxin (FXN) deficiency, e.g., Friedreich's Ataxia.

A method for delivering therapeutic proteins to the central nervous system for antibody-based therapy is provided. [Solution] A method for expressing a bivalent binding member in a cell of the nervous system, comprising the step of introducing into the cell an expression cassette encoding a polypeptide comprising an antibody heavy chain variable domain (VH), an antibody light chain variable domain (VL), and an IgG Fc region, wherein the VH and the VL form an antigen-binding site that specifically binds to a target protein, and two molecules of the polypeptide, when expressed in the cell, form a disulfide-linked homodimeric bivalent binding member specific to the target protein.

The present invention is directed to a method for treating cancer by delivering lipid-nanoparticles (LNPs) encapsulating immunostimulant mRNA and bispecific antibody mRNA to cancer cells or intratumorally. The method comprising the step of administering mRNA-encapsulated LNPs to a tumor lesion of a subject having cancer. The immunostimulant mRNA-LNP activates immune cells around tumor, which work together with mRNA-LNP encoding bispecific antibody and PBMC to effectively target local and distant metastatic tumors. Preferred immunostimulants are GM-CSF and IL-12, and its combination.

The present disclosure is directed to compositions comprising mitochondrial optogenetics-based gene therapies and their methods of use. In some embodiments, a composition described herein comprises an expression vector comprising a first nucleic acid sequence encoding a channelrhodopsin fusion protein and a second nucleic acid sequence encoding a luciferase protein. In some cases, the first nucleic acid sequence and the second nucleic acid sequence are operably linked to an expression control sequence. In some instances, the channelrhodopsin fusion protein comprises a channelrhodopsin protein linked to an inner mitochondrial membrane-mitochondrial localization signal (IMM-MLS). In some implementations, when the expression vector is expressed, the luciferase protein is localized to the cytosol. In some cases, the IMM-MLS comprises a leading sequence from a mitochondrial inner membrane protein selected from ABCB10, ABCB140, Cytochrome C, and renal outer medullary potassium channel (ROMK).

Provided herein are compositions and methods for treating or preventing dilated cardiomyopathy (DCM) in a subject in need thereof, e.g., through correcting one or more point mutations at the RBM20 locus using CRISPR-associated base editing.

Provided are guide RNAs targeting the C9orf72 gene and CRISPR / Cas systems, lipid nanoparticles or viral vectors comprising such CRISPR / Cas systems, and cells or animals comprising such CRISPR / Cas systems. Also provided are methods for suppressing transcription from the C9orf72 exon 1A transcription start site and / or for suppressing transcription of sense and / or antisense transcripts comprising hexanucleotide repeat expansion sequences in the C9orf72 gene using a CRISPR / Cas system, and the use of a CRISPR / Cas system in prophylactic and therapeutic applications for the treatment and / or prevention of C9orf72 hexanucleotide repeat expansion-related diseases and / or for ameliorating at least one symptom associated with such diseases.

Provided herein are targeting peptides and vectors containing a sequence that encodes the targeting peptides that deliver agents to specific substructures in the brain. Provided herein are viral vectors each comprising a modified capsid, wherein the modified capsid comprises at least one amino acid sequence that targets the viral vector to a distinct brain structure.

The present invention relates to a polynucleotide comprising two inverted terminal repeats (ITRs), an hGRK1 promoter, an SV40 late intron, a transgene encoding an RPGR polypeptide, and an SV40 late polyA.

The present disclosure provides pharmaceutical compositions containing nucleic acid molecules encoding PEDF which are codon-optimized, as well as methods for increasing the level of PEDF in the treatment or prophylaxis of retinal degenerative diseases, such as age-related macular degeneration (AMD), or other neurodegenerative diseases.

Provided is a recombinant adeno-associated virus (rAAV) or recombinant lentivirus, comprising an expression cassette in the genome, the expression cassette comprises a polynucleotide encoding thiamine pyrophosphokinase (TPK), which is operatively linked to a promoter. Also provided are also a pharmaceutical composition comprising the rAAV or recombinant lentivirus, and use of the rAAV, recombinant lentivirus and the pharmaceutical composition in the preparation of a medicament for treating or preventing Alzheimer's disease.

An object of the present invention is to provide a biocompatible carrier material capable of locally releasingparticles. The present inventors have found that by using a non-gelling polymer formed by reversibly bonding a plurality of hydrophilic polymer units as a carrier material, it is possible to locally release particles to an affected part such as an ulcer surface, thereby enhancing gene transduction specificity and reducing off-target effects.

An expression cassette for expressing a transgene in hepatocytes is provided herein, wherein the transgene encodes an ARSA polypeptide. Also provided is a method of treating metachromatic leukodystrophy (MLD). Further provided herein are vectors (e.g., rAAV vectors), viral particles, pharmaceutical compositions, and kits for expressing the ARSA polypeptide in an individual in need thereof.

The present disclosure provides orthogonal chimeric cytokine receptor / orthogonal cytokine pairs and compositions and methods for modified immune cells or precursors thereof (e.g., modified T cells) comprising an orthogonal chimeric cytokine receptor (e.g., an oIL2R-IL9R chimeric receptor) and a chimeric antigen receptor (CAR) or a T cell receptor (TCR). The present disclosure further provides an oncolytic adenoviral vector comprising a nucleic acid sequence encoding an orthogonal cytokine (e.g., oIL2), as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof.

This invention describes compositions and methods for the delivery of fully human post-translationally modified therapeutic monoclonal antibodies, or their antigen-binding fragments, that bind to C5, to human subjects for ocular indications, particularly for the treatment of AMD. The nucleotide sequence encoding the antibody is delivered via an rAAV vector that targets ocular tissue cells for transgene expression.

Congenital hereditary endothelial dystrophy (CHED) is an autosomal recessive condition affecting the corneal endothelial cells, which function to maintain corneal clarity. Currently there is no highly efficacious treatment available for CHED caused by SLC4A11 gene mutations. The invention disclosed herein includes mammalian vectors for use in the treatment of Congenital hereditary endothelial dystrophy and methods for using such vectors.

This invention provides drugs and methods for preventing or reversing hearing loss. [Solution] A composition comprising at least two different nucleic acid vectors, each of which comprises a coding sequence encoding a different portion of the otoferrin protein, and the use of these compositions for treating hearing loss in a subject are provided herein. This disclosure is based on the discovery that a composition comprising at least two different nucleic acid vectors, each of which comprises a coding sequence encoding a different portion of the otoferrin protein, can be used to generate a sequence encoding an active otoferrin protein (e.g., full-length otoferrin protein) in mammalian cells, thereby enabling the treatment of asymptomatic sensorineural hearing loss in a subject in need.

This application provides a novel differentiation factor for direct cross-differentiation from somatic cells to motor neurons, a composition containing the differentiation factor, a method for direct cross-differentiation using the composition, and uses for the novel differentiation factor. [Solution] A composition for direct cross-differentiation from somatic cells to induced motor neurons, the composition comprising (A) the Gsta4 protein or nucleic acid coding therefor; and (B) one or more proteins selected from Ascl1, Brn2, Myt1L, Hb9, ISL1, Lhx3, Ngn2 and NeuroD1 or nucleic acid coding therefor; and further comprising a viral capsid for transmitting (A) or (B).

Providing nucleic acid molecules and other components for targeting the CYP4V2 gene. [Solution] This disclosure provides nucleic acid molecules (e.g., sgRNA or gRNA molecules) for targeting the CYP4V2 gene encoding the cytochrome P450, family 4, subfamily V, polypeptide 2 protein, and donor nucleic acid molecules specific to the CYP4V2 gene. The use of these for targeting, disrupting and / or modifying mutations (e.g., c.802-8_810del17insGC mutation) of the human CYP4V2 gene, and for the treatment of crystallin retinopathy (BCD), is also provided.

A method for treating a subject with tauopathy by administering either full-length p38γ isoform 2 or its constitutively active mutant p38γ D179A, which promotes phosphorylation of tau at threonine in the sequence SSPGSPGTPGSRSR, which corresponds to amino acid position threonine 205 (T205) in human tau. The method also includes introducing a phosphomimetic of phosphorylated tau, wherein the phosphorylated tau is phosphorylated at threonine in the sequence SSPGSPGTPGSRSR. The treatment method results in improved cognitive performance and reduced tau aggregates and neurofibrillary tangles in a subject suffering from cognitive impairment associated with a tauopathy.

Provided herein are compositions and methods of utilizing engineered viral capsid for therapeutic delivery. Also provided herein are methods of using the provided compositions and methods for delivering therapeutic for treating diseases.

The present inventors found an inhibitory neuron-specific promoter sequence which, although having a shorter length than the mGAD65 promoter, does not impair any of the promoter activity, specificity for inhibitory neurons, and gene expression efficiency, which is specifically a promoter consisting of DNA having a promoter activity, comprising: a base sequence of a Dlx1 binding site and / or a Dlx2 binding site in a glutamic acid decarboxylase (GAD) promoter; and a base sequence of a region ranging from a 5' end of exon 1 to a transcription start site (TSS) in a glutamic acid decarboxylase (GAD).

This invention discloses the application of a PDLIM2 gene overexpression viral vector in the preparation of drugs for treating podocyte disease, wherein the nucleotide sequence of the PDLIM2 gene is shown in SEQ ID NO:1. This invention is the first to discover and verify the core role of the PDLIM2 gene in podocyte protection, confirming its significant downregulation in DKD and FSGS disease models, and demonstrating through functional experiments that PDLIM2 overexpression can effectively stabilize the podocyte cytoskeleton, inhibit apoptosis, and reduce proteinuria, thus establishing it as a key target gene for the treatment of podocyte disease. This invention is the first to intervene at the gene level in the core link of podocyte damage—cytoskeleton stability. By specifically upregulating the expression of PDLIM2 in podocytes, it directly enhances their intrinsic cytoskeleton support and anti-damage ability, achieving a fundamental shift in treatment strategy from "symptomatic support" to "causal repair."

A recombinant adeno-associated virus (rAAV) vector for the treatment of proteinopathy in the central nervous system, comprising one or two of the following: (a) a nucleotide sequence encoding progranlin (PGRN) and (b) a nucleotide sequence encoding stasmin-2 (STMN2). Also disclosed are codon-optimized coding sequences of PGRN and / or STMN2, and expression cassettes, vectors, and viral particles containing them.

This document relates to AAV vectors (e.g., AAV2 vectors). For example, AAV vectors (e.g., AAV2 vectors) containing an AAV capsid polypeptide that includes an amino acid sequence set forth in any one or more of Tables 1A-1L (or a variant thereof) or according to Formula A based on such a set forth sequence, such AAV capsid polypeptides, nucleic acid molecules encoding such vectors, nucleic acid molecules encoding such AAV capsid polypeptides, host cells containing and / or expressing such nucleic acid molecules, and methods and materials for making or using such vectors and / or AAV capsid polypeptides are provided.

Provided are methods for treating an ocular neovascular disease in an individual by reducing Auction of central subfoveal thickness (CST) or central retinal thickness (CRT), comprising administering a unit dose of recombinant adeno-associated virus (rAAV) particles to an eye of the individual, wherein the rAAV particles comprise: a) a nucleic acid encoding a polypeptide comprising an amino acid sequence with at least about 95% identity to the amino acid sequence of SEQ ID NO: 35 and Ranked by AAV2 inverted terminal repeats (ITRs), and b) an AAV2 capsid protein comprising an amino acid sequence LGETTRP (SEQ ID NO: 14) inserted between positions 587 and 588 of the capsid protein, wherein the amino acid residue numbering corresponds to an AAV2 VP1 capsid protein.

Provided herein are methods of treating glioblastoma including administering to a subject having glioblastoma a therapeutically effective amount of a pharmaceutical composition comprising 4-1BBL, optionally in combination with recombinant IL-12. The 4-1BBL can be provided to the subject via an adeno-associated virus, for example AAV-F, and the IL-12 can be provided by intratumoral injection.

Methods of treating diseases associated with pathologic neuronal cells are provided. Accordingly, there is provided a method of treating a disease associated with pathologic neuronal cells characterized by aberrant excitability comprising: (a) administering into a first neural region of the subject a therapeutically effective amount of a polynucleotide encoding a bistable type II opsin attached to a heterologous ER export signal and / or membrane trafficking signal which enables trafficking of said bistable type II opsin to axon and / or dendrite terminals, wherein said first neural region comprises cell bodies of said pathologic neuronal cells; and (b) exposing a second neural region of said subject to light in a wavelength that activates said bistable type II opsin, wherein said second neural region comprises axon or dendrite terminals of said pathologic neuronal cells associated with a symptom of said disease, and wherein said first neural region and said second neural region are distinct.

Provided herein are expression cassettes for expressing a transgene in a cell, wherein the transgene encodes a disorder-associated polypeptide. Also provided are methods of treating various neurodegenerative disorders. Further provided herein are vectors (e.g., rAAV vectors), viral particles, pharmaceutical compositions, and kits for expressing a disorder-associated polypeptide in an individual in need thereof.

Adeno-associated virus (AAV) vectors are provided. The vectors are modified by the covalent coupling of at least one compound comprising a lactam moiety (e.g., β-lactam) to at least one amino group of an amino acid residue of the capsid of the AAV vectors. The AAV vectors are useful in transducing a cell, especially for gene therapy.