120 results about "Adeno-associated virus" patented technology

Disclosed are methods and compositions relating to antisense therapy for treating epilepsy, such as a focal epilepsy and temporal lobe epilepsy, in a subject in need thereof by targeting GRIK2 mRNA. In particular, the disclosure provides methods for treating symptoms (e.g., seizures) of epilepsy in a subject by administering a particular dose in a defined volume and in a specific route of administration of an inhibitory ribopolynucleotide or adeno-associated viral vector encoding the same, which is capable of inhibiting expression of GRIK2.

The present disclosure provides a construct comprising a coding sequence operably linked to a promoter, wherein the coding sequence encodes a vascular endothelial growth factor (VEGF) binding agent or a portion thereof. In some embodiments, a construct is an AAV construct. In some embodiments, an AAV construct is a part of an AAV particle. Compositions comprising constructs and AAV particles described herein can be useful in treating hearing loss, for example, hearing loss associated with vestibular schwannoma.

Provided herein are pharmaceutical compositions comprising a recombinant adeno-associated virus (AAV), a salt excipient or buffer, a sugar, and a surfactant. Also provided herein are methods for treating or preventing a disease in a subject in need thereof by administering to the subject a therapeutically effective amount of the pharmaceutical compositions.

Provided is a recombinant adeno-associated viral (rAAV) vector comprising one or two of (a) to (c): (a) a nucleotide sequence encoding aromatic L-amino acid decarboxylase (AADC), (b) a nucleotide sequence encoding glucocerebrosidase (GBA1); and (c) a nucleotide sequence encoding a neurotrophic factor (NTF), such as cerebral dopamine neurotrophic factor (CDNF) or glial cell derived neurotrophic factor (GDNF), for treating neurodegenerative disorders, particularly Parkinson's disease (PD), Multiple system atrophy (MSA), Gaucher's disease (GD), and other proteinopathies. Also provided herein are viral particles comprising the rAAV vector, a pharmaceutical composition comprising the viral particles, and uses thereof.

Disclosed herein are nucleic acid molecules and compositions of preparing recombinant adeno-associated viruses (rAAV) and uses thereof. Specifically, two-plasmid systems are provided for efficient rAAV production.

Provided is an AAV vector capable of expressing a human Mef2c gene in the brain. Specifically, provided are an adeno-associated virus vector capable of expressing a full-length MEF2C protein, and the use thereof. The adeno-associated virus vector can significantly ameliorate the social deficit symptoms of mice with Mef2c gene deletion.

The present invention relates to: an AAV-based PDE6B viral vector for treating retinitis pigmentosa, the AAV-based PDE6B viral vector containing a tissue-specifically expressed PDE6A promoter; and a use of thereof, and provides a gene therapy for treating retinitis pigmentosa caused by PDE6B gene deficiency. The in vivo therapeutic efficacy of seven types of AAV5-PDE6B vectors was confirmed using an AAV by using a PDE6A promoter that is tissue-specifically expressed in photoreceptor rod cells that develop retinitis pigmentosa. An AAV5-PDE6A-450-PDE6B vector was selected as a candidate due to exhibiting strong tissue-specific expression in photoreceptor rod cells under even off-target conditions, unlike the gene expression characteristics of an AAV5-CMV-PDE6B vector, and was tested so as to be usable in the development of a gene therapeutic agent for treating PDE6B-deficient retinitis pigmentosa patients. Therefore, the present invention, related to AAV5-PDE6B for retinitis pigmentosa treatment and containing a tissue-specifically expressed PDE6A promoter, provides retinitis pigmentosa patients with an important treatment option having improved safety, and can be expected to have fundamental therapeutic effects compared to conventional treatments.

A recombinant adeno-associated virus (rAAV) vector comprising an AAVhu68 capsid produced in a production system comprising a nucleotide sequence of SEQ ID NO: 1, or a sequence at least 75% identical thereto which encodes SEQ ID NO:2. The AAVhu68 capsid comprises subpopulations of highly deamidated asparagine residues in asparagine-glycine pairs in the amino acid sequence of SEQ ID NO: 2. Also provided are compositions containing the rAAV and uses thereof. Additionally, rAAV having an engineered AAV capsid comprising at least one subpopulation of vp1 or vp2 proteins having a Val at amino acid position 157 with reference to the AAVhu68 vp1 numbering are provided.

The invention provides application of a Parp7 overexpression reagent in preparation of drugs for treating hypertensive nephropathy and protecting acute kidney injury caused by sepsis, and belongs to the technical field of biological medicine. According to the application disclosed by the invention, the pathological processes of the two diseases can be effectively relieved by increasing the expression level of Parp7 in the renal proximal tubule epithelial cells in a targeted manner. The invention further provides an adeno-associated virus vector comprising a renal proximal tubule epithelial cell specific promoter, a nucleotide sequence encoding Parp7 protein, and a transcription termination signal sequence. Experiments show that the strategy can significantly improve renal function indexes, relieve pathological injury of kidney tissues and inhibit local inflammatory response in an animal model. The invention provides a brand new target spot and gene therapy strategy for the treatment of hypertensive nephropathy and sepsis acute kidney injury.

Provided are methods for inserting a large gene / polynucleotide between about 4.5Kb and about 8Kb and lacking a selection marker into a target genomic position in a cell by delivering the gene / polynucleotide by two AAV vectors in the presence of a p53-binding protein 1 (53BP1) inhibitor and a DNA-dependent protein kinase catalytic subunit (DNA- PKcs) inhibitor. The disclosed methods improve large gene insertion by at least 10-fold and obviate the need for a selection marker in the vector design, thereby providing more room in the AAV vector for gene delivery.

The present application relates to the application of long-chain non-coding RNA HILAR inhibitor in the preparation of drugs for preventing or / and treating lung adenocarcinoma metastasis. The present application provides specific intervention means for HILAR, and verifies the effectiveness of inhibiting lung adenocarcinoma metastasis: after the expression of HILAR is targeted and silenced in vitro by small interfering RNA technology, the invasion ability of lung adenocarcinoma cells is significantly inhibited, and the metastasis phenotype is obviously reversed; more importantly, through the delivery of short hairpin RNA by adeno-associated virus vector, the formation and development of lung metastasis are effectively reduced in a lung adenocarcinoma metastasis mouse model, and the in vivo imaging shows that the tumor luminescence signal intensity of the experimental group is continuously lower than that of the control group, and the overall survival condition of the animal is improved.

This invention discloses a first adeno-associated virus (AAV) vector, a composition comprising a first AAV vector and a second AAV vector, and the application thereof. The first AAV vector contains a nucleotide sequence encoding a fusion protein encoding a Magnet photosensitizing protein and a Dre recombinase fragment, wherein the Magnet photosensitizing protein comprises nMag and pMag, and the Dre recombinase fragment comprises Dre… 1‑246 Fragments and Dre 247‑342 The Magnet photosensitive protein and the Dre recombinase fragment are linked by linkers L4 and T2A. The structure of the fusion protein is shown below: Dre 1‑246 Fragment - L4 - nMag - T2A - pMag - L4 - Dre 247‑342 The first fragment; the second AAV vector carries the Rox sequence and the target protein gene sequence. The AAV vector expression system of this invention is stable and has high expression efficiency. By controlling light conditions, it can achieve precise control of target protein expression within specific time and space, and is widely used in gene editing technology development, gene function research, and the development of gene therapy drugs.

This present disclosure is directed to Ligating monomers and polymers prepared therefrom are described. Filter elements including the ligating polymers are further described as are the uses thereof for separation of adeno-associated viruses containing a DNA payload ("full AAV") from adeno-associated viruses without a DNA payload ("empty AAV").

Provided herein are methods of detecting and quantifying replication competent adeno-associated virus (rcAAV) in a recombinant adeno-associated virus (rAAV) sample comprising multiplex digital PCR (dPCR). Also provided herein are methods of performing quality control on an rAAV product.

The application discloses a fusion protein CHC targeting soluble IL-17RD, a preparation method and application thereof. The fusion protein CHC is formed by connecting and fusing two sIL-17RD neutralizing nanobodies CQ5 and CQ13 with human serum albumin (HSA) through a linker, and the structure is CQ5-Linker-CHC-Linker-CQ13, and the amino acid sequence is shown as SEQ ID NO. 1. The application further provides a gene sequence coding the fusion protein and an adeno-associated virus AAV-PHP.eB carrier containing the gene. The neutralizing nanobody fusion protein can specifically bind and neutralize the biological function of sIL-17RD, regulate the brain vascular endothelial cell homeostasis by directly inhibiting the inflammatory response of brain vascular endothelial cells induced by TNF-alpha and indirectly inhibiting the activation of microglial cells. The application can be used for treating or preventing neurodegenerative diseases such as Alzheimer's disease, and has the effects of protecting vascular injury, improving learning and memory and cognitive impairment, reducing beta-amyloid plaque deposition, reducing neuron loss and glial cell activation and the like.

This application relates to the fields of gene therapy and molecular biology. More specifically, the present invention relates to an isolated altered VP1 protein of adeno-associated virus serotype 5 (AAV5) capsid comprising one or more amino acid substitutions as compared to the VP1 protein of wild-type AAV5 capsid, which increase transduction efficiency, as well as to a capsid and a vector based thereon.

A potassium channel gene treatment method for treating Parkinson's disease. A recombinant adeno-associated virus (AAV) nucleotide sequence comprises a nucleotide sequence encoding an inwardly rectifying potassium channel Kir. An AAV vector is used to deliver an inwardly rectifying potassium channel (Kir) gene to the subthalamic nucleus, such that excitability of neurons of the subthalamic nucleus is reduced, so as to alleviate symptoms such as motor deficits caused by excessive excitation of the subthalamic nucleus in patients with Parkinson's disease.

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 Table 1A (or a variant thereof) or Formula A, an amino acid sequence set forth in Table 1B (or a variant thereof) or Formula B, or an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C, 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 is a method for producing a protein / nucleic acid complex which comprises a capsid protein derived from an adeno-associated virus and a genomic nucleic acid having at least one inverted terminal repeat sequence and has infectiousness to mammals. The genomic nucleic acid further includes a target nucleic acid that encodes a target protein. The method comprises: (a-1) a step for providing an isolated first nucleic acid that comprises a linear single-stranded nucleic acid, a linear double-stranded nucleic acid, or a circular single-stranded nucleic acid and includes at least one inverted terminal repeat sequence and a target nucleic acid that encodes a target protein; (a-2) a step for providing an isolated first nucleic acid that includes at least one inverted terminal repeat sequence and a target nucleic acid that encodes a target protein; and (b) a step for bringing a first protein into contact with the first nucleic acid in a solvent to form the protein / nucleic acid complex.

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.

The application relates to a method for detecting GDNF protein activity in vitro, comprising the following steps: a) contacting an adeno-associated virus (AAV) containing a nucleotide sequence encoding a GDNF protein with first cells expressing an adeno-associated virus receptor (AAVR), culturing the first cells, and collecting culture supernatant; b) incubating the culture supernatant in step a) with second cells, wherein the second cells are reporter gene cells; and c) detecting an indicating signal generated by the reporter gene, wherein the reporter gene cells contain a GFR alpha 1 expression element, a RET expression element, a transcription response module and a reporter gene module; the transcription response module contains a GAL4-ELK1 fusion protein and / or a nucleic acid encoding the fusion protein; and the reporter gene module contains a nucleic acid encoding a GAL4 response element and a reporter gene.

The present invention relates to regulatable adeno-associated virus (AAV) vectors as well as to their use in gene therapy. It further relates to corresponding nucleic acid molecules, host cells, non-human transgenic animals, pharmaceutical compositions and kits.

The application discloses application of an ACSS1 gene in preparation of a drug for promoting growth of neuron axons in vitro, and belongs to the technical field of biological medicines. The application knows that expression of the ACSS1 protein presents a progressive downward trend with time passing after injury through construction of a spinal cord injury model and collection of spinal cord tissues, and then the adeno-associated virus is used to overexpress the ACSS1 in neuron primary cells, and the result shows that the length of neuron axons is significantly increased after overexpression of the ACSS1. Therefore, a substance for promoting expression of the ACSS1 gene can be used as a reagent for preparing a drug for promoting growth of neuron axons in vitro.

The present invention provides a group of compounds for the sequestration of Adeno-associated virus (AAV) and adenovirus (AdV) neutralizing antibodies (NAbs) in a patient. The compounds comprise an inert backbone conjugated with at least one recombinant peptide comprising an epitope. The epitope is a conserved epitope that is targeted by human anti-AAV or anti-AdV NAbs. The backbone where the conserved epitope is conjugated to is a poly-lysine (PLys) or poly-acrylamide (PAA) backbone, among others. Also provided is a pharmaceutical composition comprising this type of compounds, as well as a method for use to treat an individual to inhibit the immune reaction against an AAV or AdV-based therapy. It is also possible to use synthetic compounds for an in vitro detection of anti-AAV or anti-AdV NAbs in a sample.

Provided herein are targeting peptides and vectors containing a sequence that encodes the targeting peptides that deliver agents to specific substructures in the brain. Specifically, the targeting peptide is a component of a modified, sequence-specified adeno-associated virus (AAV) capsid protein further wherein the brain substructure may be the globus pallidus, putamen, internal capsule, caudate, claustrum, substantial nigra, motor cortex, insula,.temporal cortex, thalamus, hippocampus, subiculum, and deep cerebellar nuclei.

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.

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 application relates to a kind of cytoplasm-specific expression PPM1K gene delivery system and its preparation method and application, belong to gene delivery system preparation technical field.The gene delivery system is preferably adeno-associated virus (AAV), and its preparation method specifically includes the following steps: PPM1K gene or its functional variant is inserted into vector, detectable label is added at C-terminal, and recombination plasmid is formed;Recombinant plasmid is transformed into competent e. coli and is amplified, after plasmid is screened, recombination AAV plasmid is obtained;Recombinant AAV plasmid, auxiliary plasmid and capsid plasmid are co-transfected into packaging cell using transfection reagent, after transfection, cell and culture supernatant are collected, freeze-thaw buffer is added repeatedly freeze-thaw, and cell lysate is obtained;After centrifugation of cell lysate, supernatant is taken, and purified filtration is carried out.The present application realizes the cell compartment specificity expression of treatment gene by vector design, and shows significant treatment effect and safety advantage.

This document relates to AAV vectors (e.g., AAV2 vectors). For example, it provides AAV vectors (e.g., AAV2 vectors) containing AAV capsid polypeptides, 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 preparing or using such vectors and / or AAV capsid polypeptides comprising the amino acid sequences shown in Table 1A (or variants thereof) or Formula A, Table 1B (or variants thereof) or Formula B, or Table 1C (or variants thereof) or Formula C.