1674 results about "Adeno-associated virus" patented technology

The disclosure provides compositions and methods for the preparation, manufacture and use of an adeno-associated virus (AAV) particle for the vectorized delivery of an antibody molecule that binds to tau.

The disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid protein variants.

The disclosure relates to compositions and methods for modulating, e.g., reducing or eliminating, the expression of ATXN2 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 diagnosed with, suspected of having, or having spinocerebellar ataxia type 2 (SCA2) or another ATXN2-related disorder.

The disclosure relates to compositions and methods for modulating, e.g., reducing or eliminating, the expression of mutated DMPK 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 myotonic dystrophy type 1 or another DMPK-related disorder.

The invention belongs to the technical field of nano antibodies, and particularly relates to a nano antibody specifically bound with AAV9 and application of the nano antibody. The nano antibody provided by the invention can be specifically combined with the AAV9 adeno-associated virus without being combined with other AAV serotypes such as AAV2, AAV5 and AAV8, so that high-sensitivity and high-specificity detection of the AAV9 adeno-associated virus is realized. In practical application, the nano-antibody coupled solid-phase carrier provided by the invention is adopted as an affinity filler, the AAV9 adeno-associated virus can be effectively captured and mildly eluted, the virus purification and recovery effects are effectively improved, and the nano-antibody coupled solid-phase carrier is suitable for high-purity recovery of the AAV9 adeno-associated virus.

Methods are disclosed for delivering a composition comprising an adeno-associated virus (AAV) to one or more kidney cell types in a subject with or without immunity against AAV, including locally delivering to the kidney of the subject an adeno-associated virus (AAV) comprising a genome and an AAV capsid protein via renal pelvic injection, wherein the renal pelvic injection comprises direct renal pelvic injection or retrograde transureteral renal pelvic injection. Methods are also disclosed for treating a kidney disorder in a subject with or without immunity against AAV, comprising locally delivering to the kidney of the subject via renal pelvic injection, including direct renal pelvic injection and retrograde transureteral renal pelvic injection, an adeno-associated virus (AAV) comprising a genome and an AAV capsid protein, wherein the genome encodes a therapeutic agent that treats the kidney disorder in the subject. The AAV can be AAVKP1, AAVKP2, AAVKP3, AAVDJ, AAV2G9, AAV2.7m8, AAV3, AAVLK03, or AAVShH10.

Disclosed herein are genetically engineered cells for AAV production. The genetically engineered cell comprises molecular systems for temporal control of expression of genes required for AAV production. Also disclosed herein are methods of using genetically engineered cells for AAV production.

The invention relates to application of an MYZAP overexpression vector in preparation of a medicine for preventing and treating MIRI, and belongs to the technical field of biological medicine. In order to solve the problem that application of gene drugs in prevention and treatment of myocardial ischemia reperfusion injury is limited, the invention provides application of an MYZAP gene overexpression recombinant vector in preparation of drugs for prevention and treatment of myocardial ischemia reperfusion injury, and the MYZAP gene overexpression recombinant vector is an adeno-associated virus vector AAV9-MYZAP for overexpressing MYZAP. Experiments prove that MYZAP overexpression can improve the cardiac function after myocardial ischemia reperfusion, reduce the occurrence rate of arrhythmia and improve the functions of sodium ion channels, potassium ion channels and calcium ion channels of myocardial cells. On the basis, the invention further provides a medicine for preventing and treating myocardial ischemia reperfusion injury, a new strategy is provided for gene therapy of myocardial ischemia reperfusion injury, and the medicine has a wide clinical application prospect.

The disclosure provides compositions and methods for the preparation, manufacture and use of an adeno-associated virus (AAV) particle for the vectorized delivery of an antibody molecule that binds to tau.

The invention belongs to the technical field of gene engineering and biology, discloses a modified adeno-associated virus AAV-8 serotype for retina wide targeting and expression, and further relates to construction and application of the modified type. 10 amino acid sequences as shown in SEQ ID NO.3 are inserted between the 590th amino acid and the 591th amino acid of an AAV-8 serotype capsid protein sequence as shown in SEQ ID NO.2, the first, second and tenth amino acids are protected amino acids, and the third to ninth amino acids are amino acid sequences obtained by screening. The modified serotype disclosed by the invention is stronger in fluorescence effect after infection and can be obviously and intuitively observed, an exogenous gene can be widely and efficiently expressed in a specific targeted tissue retina whole region, and the expression efficiency is greatly improved under the condition of using the same virus amount. And compared with a wild serotype, the serotype has better and wider targeted tissue expression and less non-targeted tissue expression.

The disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid protein variants.

The present invention relates to the field of biomedicine, and discloses a fusion-type adeno-associated virus and its application in ear diseases and ophthalmic diseases. The fusion-type adeno-associated virus comprises a fusion peptide segment or a variant thereof formed by fusing peptide segments of serotypes AAV1, 2, 6 and 7, which can efficiently transduce hair cells and / or supporting cells in the cochlea, promote the regeneration of inner hair cells, and help restore hearing. The adeno-associated virus can also efficiently infect the RPE layer and is used for the treatment of ophthalmic diseases. As a safe vector, the fusion-type adeno-associated virus has broad application prospects in the treatment of ear diseases or ophthalmic diseases.

The disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid protein variants.

The present disclosure provides nucleic acid molecules comprising a first inverted terminal repeat (ITR), a second ITR, and a genetic cassette encoding a miRNA and / or a therapeutic protein. In certain embodiments, the therapeutic protein comprises a clotting factor, e.g., a FVIII polypeptide, a FIX polypeptide, or a fragment thereof. In some embodiments, the first ITR and / or the second ITR is an ITR of a non-adeno-associated virus (AAV). The present disclosure also provides methods of treating bleeding disorders such as hemophilia comprising administering to the subject the nucleic acid molecule or a polypeptide encoded thereby.

The invention belongs to the field of biological medicines, and particularly relates to a method for inhibiting osteogenic differentiation of human aortic valve interstitial cells (hVICs), namely, N-acetyltransferase 10 (NAT10) is silenced in vivo and in vitro by a biological method, and the NAT10 is over-silenced in a mouse body by adeno-associated viruses according to the method, so that the result shows that the mouse aortic valve calcification can be inhibited by the silencing of the NAT10, and the osteogenic differentiation of the human aortic valve interstitial cells (hVICs) can be inhibited. NAT10 is silenced in hVICs through adenovirus, and it is found that NAT10 silencing can inhibit osteogenic differentiation of hVICs, so that valve calcification is delayed or inhibited. The invention further provides a method for preventing and treating aortic valve calcification by inhibiting the NAT10 protein expression level, and a new non-surgical treatment scheme is provided for preventing and treating calcified aortic valve diseases.

The invention provides application of macrophage PHGDH in preparation of a TAK1 inhibitor, and belongs to the technical field of biological medicine. The invention finds that the PA-induced inflammation can be promoted by knocking down the PHGDH in the macrophage. In addition, the macrophage specific PHGDH is combined with TAK1, and the interaction between TAK1 and TAB1 is inhibited, so that the activation of TAK1 and downstream NF-kB and MAPK signal transduction are inhibited. Development of metabolic dysfunction related steatohepatitis MASH caused by medullary system PHGDH knockout can be slowed down by inhibiting TAK1 activation. What's more important is that the MAFLD is reduced by the overexpression of the PHGDH in the adeno-associated virus mediated liver macrophages. The invention discovers that the macrophage PHGDH is a promising medicine for treating MAFLD (MAFF-induced leukemia disease).

The invention relates to application of an MYZAP overexpression recombinant vector in preparation of a medicine for preventing and treating arrhythmia, and belongs to the technical field of biological medicines. In order to solve the problem that application of gene drugs in prevention and treatment of arrhythmia after myocardial infarction is limited, the invention provides application of a myocardial microbelt adhesion protein MYZAP overexpression recombinant vector in preparation of drugs for prevention and treatment of arrhythmia, and the MYZAP overexpression recombinant vector is an adeno-associated virus vector AAV9-MYZAP of an overexpression MYZAP gene. In-vivo experiments prove that MYZAP overexpression can reduce the occurrence of arrhythmia after myocardial infarction by increasing the content of MYZAP protein in cardiac myocardial cells, and improve cardiac functions and cardiac electrical conduction disorders after myocardial infarction. On the basis, the invention further provides a medicine for preventing and treating arrhythmia after myocardial infarction, a new strategy is provided for gene therapy of arrhythmia after myocardial infarction, and the medicine has a wide clinical application prospect.

The present invention relates to an exogenous target gene expression cassette for delivering an exogenous target gene to the retina, in particular AIPL1 to retinal pigment epithelial cells and photoreceptor cells, comprising an IRBP enhancer sequence, a rhodopsin kinase (RK) promoter sequence and a CAG intron sequence, which are operatively linked, and an exogenous target gene. The present invention also relates to a recombinant adeno-associated viral vector comprising a viral capsid comprising a capsid protein or a capsid protein variant and a viral vector genome comprising an expression cassette encoding for specifically expressing an exogenous target gene in retinal pigment epithelial cells and photoreceptor cells. The recombinant adeno-associated virus vector can be used for relieving or treating retinal degenerative eye diseases by intravitreal administration or subretinal administration.

The disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid protein variants.

The invention relates to the field of biological medicine, in particular to an adeno-associated virus as well as a preparation method and application thereof. The capsid protein of the adeno-associated virus AAV-ACM205 provided by the invention comprises a wild type AAV2 capsid protein or a variant of the wild type AAV2 capsid protein, the wild type AAV2 capsid protein or the variant of the wild type AAV2 capsid protein comprises peptide fragments with amino acid sequences as shown in SEQ ID NO.6 and SEQ ID NO.7, and a random peptide fragment is inserted between the SEQ ID NO.6 and the SEQ ID NO.7. The adeno-associated virus vector AAV-ACM205 provided by the invention can mediate a target gene to be specifically and efficiently expressed in hair cells in cochlea of an adult mouse under the condition of semicircular canal injection; the adeno-associated virus vector AAV-ACM205 mediated target gene expression is more flexible and efficient than that of a traditional transgenic method, is convenient to apply and low in cost, and has a wide prospect in ear disease gene therapy.

The invention belongs to the technical field of nano antibodies, and particularly relates to a nano antibody specifically bound with AAV2 and application of the nano antibody. The nano antibody provided by the invention can be specifically combined with the AAV2 adeno-associated virus without being combined with other AAV serotypes such as AAV5, AAV8 and AAV9, so that high-sensitivity and high-specificity detection of the AAV2 adeno-associated virus is realized. In practical application, the nano antibody coupled solid-phase carrier provided by the invention is adopted as an affinity filler, the AAV2 adeno-associated virus can be effectively captured and mildly eluted, the virus purification and recovery effects are effectively improved, and the nano antibody coupled solid-phase carrier is suitable for high-purity recovery of the AAV2 adeno-associated virus.

The present invention relates to an adeno-associated virus (AAV) capsid protein variant having an amino acid mutation at the 328th to 331st amino acid residues of the AAV capsid protein relative to the 328th to 331st amino acid residues of the parent AAV capsid protein, for example, an amino acid sequence as shown in SEQ ID NO: 4 to replace the 328th to 331st amino acid residues of the parent AAV capsid protein wherein the amino acid position is numbered according to SEQ ID NO: 5. The invention also relates to an isolated nucleic acid encoding the AAV capsid protein variant, a nucleic acid vector comprising the same, and a host cell. The present invention also relates to a recombinant adeno-associated virus (rAAV) vector comprising said capsid protein variant, a pharmaceutical composition comprising said rAAV vector, and uses thereof in the treatment or prevention of skeletal muscle diseases.

The invention relates to the technical field of biology, in particular to a variant AAV capsid protein and a recombinant adeno-associated virus rAAV. The variant AAV capsid protein provided by the invention comprises: 1) an amino acid sequence having at least 80%, 83%, 85%, 88%, 90%, 93%, 95% and 98% of identity with an amino acid sequence as shown in SEQ ID NO.1; and 2) an amino acid sequence shown as SEQ ID NO.1, wherein the amino acid sequence comprises amino acid substituted A587D, Q588G, A589N and Q590P, and an amino acid sequence TLAVPFK is inserted after the 588th site and before the 589th site; related products constructed by the variant AAV capsid protein can be used for cross-blood-brain-barrier efficient transduction to realize drug delivery to a central nervous system to treat related diseases of the central nervous system, and meanwhile, the related products have the characteristic of remarkably reducing liver transduction.

The invention belongs to the technical field of antibody preparation, and particularly relates to a nano antibody for resisting different serotypes of adeno-associated viruses and application of the nano antibody. The nano antibody is selected from one of Nb1 to Nb24; the amino acid sequences of the heavy chain variable regions of the nano antibodies Nb1 to Nb24 are respectively shown as SEQ ID NO. 1 to 24. The nano antibody provided by the invention can sensitively and specifically bind to AAV, has excellent broad-spectrum recognition and binding capacity to various serotypes such as AAV2, AAV5, AAV8 and AAV9, and has a good application prospect in the fields of AAV immunodetection, affinity purification and the like.

The disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid protein variants.

The disclosure relates to compositions and methods for, inter alia, altering, e.g., enhancing, the level of GBA1 protein via delivery using an adeno-associated viral (AAV) capsid variant. The compositions and methods of the present disclosure are useful, inter alia, for the treatment of subjects who have, have been diagnosed with having, or are at risk of having a GBA1-related disorder, e.g., Parkinson's Disease (PD), Gaucher Disease (GD), Parkinson's Disease Dementia (PDD), Dementia with Lewy Bodies (DLB), or Lewy Body Dementia (LBD).

Described herein are compositions and kits comprising recombinant adeno-associated viruses (rAAVs) with increased transduction enrichment in the brain. The rAAV compositions described herein encapsidate a transgene, such as a therapeutic nucleic acid. Gene therapy using the rAAVs is described. Also described are methods of treating brain-related diseases and conditions.

To provide gene therapy vectors, such as adeno-associated virus (AAV) vectors, expressing a miniaturized human micro-dystrophin gene, and a method of using these vectors to express micro-dystrophin in a skeletal muscle including a diaphragm and a cardiac muscle and to protect muscle fibers from injury, increase muscle strength and reduce and / or prevent fibrosis in subjects suffering from muscular dystrophy.SOLUTION: In one embodiment, the present invention provides a rAAV vector comprising a nucleotide sequence of a muscle-specific control element and a nucleotide sequence encoding a microdystrophin protein.SELECTED DRAWING: Figure 1

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).

This present disclosure provides pharmaceutical compositions for delivering recombinant adeno-associated virus (rAAV) particles, generally comprising a buffer, a monovalent salt, a poly hydric alcohol, and a triblock copolymer surfactant.