758 results about "Viral vector" patented technology

The present invention provides a novel therapeutic drug for treating a Prom1-associated retinal disease. Specifically, the present invention provides an optimized Prom1 gene expression cassette, an rAAV viral vector, and a gene therapy drug. The drug of the present invention can specifically express the PROM1 protein in the retinal photoreceptor layer, and is suitable for the clinical treatment of a retinal disease associated with Prom1 gene mutation.

Disclosed herein are antibodies or antigen-binding fragments thereof that specifically bind to human CD19. Chimeric antigen receptors and chimeric antigen receptor transgenes comprising an antigen binding domain that specifically binds to human CD19 are also disclosed. Also described herein are immune cells, viral vectors, and other compositions containing the antibodies, the antigen binding fragments, the chimeric antigen receptors, and / or the chimeric antigen receptor transgenes.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof in the central nervous system or ex vivo. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a disease (e.g., a neurological disease), preventing a disease (e.g., neurological disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof.

The invention discloses a cell membrane protein replacement type oncolytic virus vector and application thereof. The cell membrane protein replacement type oncolytic virus vector is rhabdoviridae virus, and a nucleotide sequence for coding G protein in a genome of the rhabdoviridae virus is replaced by a nucleotide sequence for coding an antibody and a nucleotide sequence for coding a spike protein truncation of coronavirus. The invention also discloses a construction method of the cell membrane protein replacement type oncolytic virus vector for expressing the antibody, the non-replicated virus vector is used for expressing the antibody sequence for the first time, and meanwhile, the novel coronavirus cell membrane protein is embedded into the virus surface, so that the cell membrane protein replacement type oncolytic virus vector can be rapidly produced in a suspension cell in a large scale; through removal of virus cell membrane protein genes, the virus cell membrane protein genes cannot be continuously replicated in vivo, so that the safety of the virus cell membrane protein genes is ensured, the tumor immunosuppression condition is improved, and an organism can be stimulated to generate a neutralizing antibody for resisting new coronavirus while tumor cells are killed.

An active or inactivated recombinant vaccine against COVID-19 is described that comprises a Newcastle disease viral vector and a pharmaceutically acceptable carrier, adjuvant and / or excipient, characterized in that the viral vector is a virus capable of generating a cellular immune response that has a SARS-COV-2 exogenous nucleotide sequence inserted.

The invention discloses a method for quickly rescuing bovine coronavirus epidemic strains and application of the method. The bovine coronavirus SHZ isolate is subjected to efficient segmented cloning, the obtained segment and a Linker sequence are subjected to a cyclic polymerase extension reaction, and the obtained reaction product can be directly transfected to 293T cells for virus packaging without purification. Different from a traditional method, the method does not need to amplify full-length virus cDNA clone by means of bacteria and yeast, but directly obtains a sufficient amount of preliminary products through PCR, and avoids the problems of instability and low efficiency when partial sequences of a virus genome proliferate in a bacteria or yeast host. By adopting the reverse genetic system, the recombinant bovine coronavirus expressing the foreign protein is successfully rescued, a brand new technical platform is provided for dynamic visualization research of in-vivo and in-vitro replication of the virus, and an efficient and flexible tool is also provided for virology research, development of virus vector vaccines and screening of antiviral drugs.

Methods to edit genes by administering a chimeric nuclease to a cell or organism without the use of a viral vector.

Disclosed herein are methods to edit genes, for example by administering a chimeric nuclease to a cell or organism without the use of a viral vector. Some methods herein include editing DNA of a cell by contacting the cell with a nuclease comprising a Cas9 sequence, where the nuclease edits the DNA of the cell.

An engineered producer cell comprising an inactivating mutation in one or more endogenous REP binding sites is provided, as are methods for producing the engineered producer cell and using the engineered producer cell to produce a recombinant viral vector and reduce producer cell genomic DNA contamination of a recombinant adeno-associated virus vector preparation.

The present disclosure provides materials and methods related to the purification of viral vectors. In particular, the present disclosure provides peptides, compositions, adsorbents, and related methods, capable of removing process-related impurities (e.g., host cell proteins, nucleic acids, and media components) and product-related impurities (e.g., product fragments, product aggregates, and inactive forms derived from product degradation by or association with other species in the cell culture harvest) from samples during the production and purification of adenovirus.

Provided is a method for large-scale preparation of a purified preparation of a recombinant lentiviral vector at the GMP grade. The method comprises: (a) providing raw material feed liquid to be purified that comprises recombinant viral vectors; (b) carrying out a microfiltration treatment on the feed liquid to obtain a microfiltered filtrate comprising the recombinant viral vectors; (c) optionally concentrating the filtrate to obtain a concentrated filtrate; (d) purifying the filtrate obtained in the previous step by means of chromatography to obtain a crude pure product comprising the recombinant viral vectors; and (e) subjecting the crude pure product obtained in the previous step to liquid exchange and elaborate purification to obtain the purified recombinant viral vectors.

The invention discloses a recombinant adeno-associated virus vector for targeted delivery of VEGF-C (vascular endothelial growth factor-C) and application of the recombinant adeno-associated virus vector in promoting endocardial differentiation to treat coronary heart disease. The rAAV vector comprises transgene for coding VEGF-C protein or VEGF-C protein functional variant and a tissue-specific promoter operably connected to the transgene, wherein the tissue specific promoter is capable of driving the transgene to be specifically expressed in the heart endothelial cells. According to the treatment method developed by the invention, specific expression of the Vegfc gene in the heart is driven by using an ICAM2 promoter with targeting to endothelial cells, and a remarkable curative effect is shown in a myocardial infarction model mouse. The therapeutic scheme provides a new effective strategy for intervention and treatment of myocardial infarction and chronic heart failure, and has the advantages of high safety, long gene expression duration, extremely low immune response to a host and the like.

The invention relates to a genome large fragment deleted duck adenovirus B2 strain and application thereof, the duck adenovirus B2 strain is duck adenovirus B2 DAdV-B2 / delta ORF55-ORF19, and is preserved in China Center for Type Culture Collection on September 26, 2025, and the preservation number is CCTCC NO: V202568. Compared with the duck adenovirus B2 strain BGMH, the duck adenovirus B2 strain has a deletion region between ORF20 and ORF53 genes, and the duck adenovirus B2 strain is deleted by 7422 bp. According to the invention, the duck adenovirus B2 strain with the genome deleted in large fragment is found for the first time, and the deletion region of the virus is a good site for inserting an exogenous gene, so that the duck adenovirus B2 DAdV-B2 / delta ORF55-ORF19 can be used as a good virus vector to construct a recombinant virus, and the constructed recombinant virus can be stably inherited; the method can be applied to waterfowl novel recombinant virus vector vaccine research and development, waterfowl basic scientific research, gene virus vector delivery and the like, and has wide application prospect and value.

The invention discloses an SOD2 knockout cell line and application of the SOD2 knockout cell line in anti-poxvirus, and relates to the technical field of antiviral research. According to the invention, sgRNA of targeted superoxide dismutase 2 (SOD2) is designed, the sequence of the sgRNA is shown as SEQ ID NO.1-SEQ ID NO.2, then a stable SOD2 knockout human-derived non-small cell lung cancer A549 cell line is established by combining CRISPR / Cas9 gene editing with a lentiviral vector delivery technology, single-cell cloning is obtained through multiple rounds of puromycin screening, and the SOD2 gene knockout A549 cell strain is successfully constructed. Vaccinia virus Tian Tan strain infection shows that the number of plaques of SOD2 knockout cells is obviously greater than that of the plaques (about 2.3 times) of normal cell infection, and the plaques are relatively large, so that fine SOD2 has the effect of limiting intercellular transmission of poxvirus. The invention lays a foundation for research and preparation of antiviral drugs.

Aspects of the disclosure relate to compositions and methods for base editing using viral vectors. In some aspects, the disclosure provides an adenine base editor (ABE) utilizing an evolved Cas9 nickase derived from Neisseria meningitidis; and adeno-associated viruses (AAVs) comprising (or encoding) such adenine base editors. In some aspects, compositions described herein are useful for treatment of certain diseases, for example pulmonary diseases.

The invention provides a novel therapeutic drug for treating Prom1 related retinal diseases. Specifically, the invention provides an optimized Prom1 gene expression cassette, an rAAV virus vector and a gene therapy drug. The medicine provided by the invention can specifically express the PROM1 protein in a retina photoreceptor layer, and is suitable for clinical application to treatment of Prom1 gene mutation related retinal diseases.

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 invention relates to an shRNA (short hairpin Ribonucleic Acid) interference sequence of a targeted silence PCSK9 gene and a construction method and lipid-lowering application of a recombinant adeno-associated virus vector of the shRNA interference sequence. Hyperlipidaemia is a metabolic disease characterized by abnormal rising of cholesterol and triglyceride levels in blood, and the design of lipid-lowering drugs is the focus of attention to improvement of hyperlipidaemia. Proprotein convertase subtilisin / kexin type 9 (PCSK9) can be combined with a low-density lipoprotein receptor (LDL-R) and degrade the LDL-R, so that accumulation of LDL-C in blood is further promoted, and hyperlipidemia is caused. Aiming at the key target PCSK9, a specific shRNA interference sequence is designed, and a recombinant adeno-associated virus vector (rAAV) carrying the sequence is constructed by an enzyme digestion-connection method. In-vitro experiments prove that the vector can remarkably reduce the expression level of PCSK9 protein, so that the cyclic utilization of a low-density lipoprotein receptor (LDL-R) is promoted, and the concentration of low-density lipoprotein cholesterol (LDL-C) in plasma is reduced. The rAAV vector provided by the invention has the characteristics of low production cost, high transfection efficiency, lasting action time and the like, and provides a new thought for gene therapy of hyperlipidemia.

Provided are a packaging system for packaging a lentiviral vector or a retroviral vector, and a use of the packaging system. Specifically, the provided packaging system comprises a polynucleotide encoding a CAR binding molecule, wherein the CAR binding molecule can bind to a CAR. Pseudotransduction is reduced when a host cell is transduced by the lentiviral vector or the retroviral vector packaged by the provided packaging system, and the ability to transduce a target cell expressing an antigen decreases, thereby significantly improving the targeting performance of the lentiviral vector or the retroviral vector in the transduction of immune cells such as T cells.

The present disclosure provides preventing and / or treating hearing loss in an individual in need thereof comprising administering a composition comprising one or more viral vectors comprising a nucleic acid encoding COL18A1 protein, SPARC protein, and IGFBP2 protein. The present disclosure also provides method for preventing and / or treating hearing loss in an individual in need thereof comprising administering an effective amount of COL18A1, SPARC, and IGFBP2 proteins to the inner ear of the individual.

Recombinant myotropic AAV rh.74 capsids are described herein. In addition, plasmids, viral vectors, dual vector systems, cells, and compositions comprising or encoding such recombinant capsids are further described. Such recombinant polynucleotides, plasmids, viral vectors, dual vector systems, cells, and compositions may be used to treat muscle diseases or disorders, including muscular dystrophies and cardiomyopathies.

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 belongs to the technical field of medicines, and discloses application of an adeno-associated virus vector in preparation of medicines for preventing and treating RSV infection and / or diseases caused by RSV. According to the invention, a recombinant adeno-associated virus vector is adopted for the first time to construct a medicine for preventing and treating RSV infection or diseases caused by RSV infection, and based on this, the invention provides a nucleic acid molecule which comprises: (a1) a first region which comprises a first adeno-associated virus inverted terminal repeat sequence, and (a2) a second region which comprises a second adeno-associated virus inverted terminal repeat sequence; and (a2) a second region comprising a gene encoding a respiratory syncytial virus antigen; the recombinant adeno-associated virus containing the nucleic acid molecule can generate better humoral immune effect and cellular immune effect, has a certain serum neutralization effect on strains of A and B subtypes of RSV, and particularly, when the antigen is a fusion protein of the respiratory syncytial virus or a fusion protein mutant of the respiratory syncytial virus, the recombinant adeno-associated virus has a certain serum neutralization effect on the strains of A and B subtypes of the RSV. The recombinant adenovirus vector containing the nucleic acid molecule can successfully realize the expression of the F protein before RSV fusion.

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 present invention provides novel capsid variants for viral vectors that simultaneously detarget liver tissue and efficiently transduce muscular tissue.

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.

The invention discloses application of beta-nicotinamide mononucleotide in regulation and control of gene editing efficiency, belongs to the field of gene editing treatment, and finds that the beta-nicotinamide mononucleotide (NMN) can efficiently inhibit the activity of CRISPR-Cas9, CRISPR-Cas12 and CRISPR-Cas13 systems in a broad-spectrum manner for the first time. The application comprises emergency blocking of off-target effect in gene editing clinical treatment, biological safety prevention and control of a virus vector gene editing system, and CRISPR activity regulation and control of in-vitro non-diagnostic purpose. Experiments show that NMN can inhibit CRISPR-mediated gene damage and cell death in a cell model, the inhibition efficiency in an in-vitro enzyme digestion system reaches 68.7%, and cell growth or transfection efficiency is not affected. The invention provides an innovative solution for safe application of CRISPR (clustered regularly interspaced short palindromic repeats) technology, and the NMN is approved to be taken orally as a health care product, so that the NMN has extremely strong clinical application potential. Compared with the existing CRISPR (clustered regularly interspaced short palindromic repeats)-resistant protein or synthetic small-molecule inhibitor, the NMN has the advantages of endogenous property, high biocompatibility, good oral safety and the like.

Provided are compositions and method for prophylaxis and / or therapy of hearing loss or related dysfunctions, including but not limited to tinnitus, that could be ameliorated by restoring central nervous system inhibitory synapses. The compositions include polynucleotides and viral vectors that are used to express at least one GABA receptor component which may be a GABAA receptor alpha 1 subunit or GABAR receptor Ib subunit. Expression of the GABA receptor may be under control of a CaMKII promoter.

Provided herein are immortalized mesenchymal stem cells comprising a replicating recombinant retrovirus. Methods for treating a cell proliferative disorder using these immortalized mesenchymal stem cells are also provided.