1166 results about "Viral vector" patented technology

The invention discloses a neurotoxicity-free recombinant live virus vector rabies vaccine, which is prepared by replacing G protein of vesicular stomatitis virus with G protein of HEP-Flury rabies virus strain or G protein mutant of HEP-Flury rabies virus strain, and saving recombinant virus VSV-HEP-Flury by using a reverse genetic manipulation technology. The recombinant live virus vector rabies vaccine has no neurotoxicity after being inoculated. The method is free of neurotoxicity, high in safety, simple in inoculation procedure, good in immune effect and high in productivity.

Disclosed herein are chimpanzee adenoviral vectors that include neoantigen-encoding nucleic acid sequences derived from a tumor of a subject. Also disclosed are nucleotides, cells, and methods associated with the vectors including their use as vaccines.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AV 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. 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 (e.g., ocular disease), preventing a disease (e.g., ocular disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof).

The invention provides a virus particle identification method based on a negative staining electron microscope image. The deep learning and image segmentation technology is adopted to automatically identify virus particles and classify hollow and solid virus particles in the negative staining electron microscope image, so that the real heart rate and the virus particle concentration of the virus are obtained, and the requirement on the purity of a sample is low. Therefore, the production quality control process of the virus vector can be improved, and the development and optimization of gene therapy can be accelerated.

The present invention provides a self-activating small molecule induction system, cells, and applications and methods in inducing gene expression, belonging to the technical field of genetic engineering. The self-activating small molecule induction system optimizes the component composition based on the green light response system, improves the induction efficiency of the target gene through a cascade reaction, and can reduce the background leakage level, playing an important role in the induction of the target gene and having good application prospects in the field of protein expression and the production and preparation of viral vectors.

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. 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 (e.g., ocular disease), preventing a disease (e.g., ocular disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof).

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.

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 invention provides systems, methods, reagents, apparatuses, vectors, and host cells for the continuous evolution of nucleic acids. For example, a lagoon is provided in which a population of viral vectors comprising a gene of interest replicates in a stream of host cells, wherein the viral vectors lack a gene encoding a protein required for the generation of infectious viral particles, and wherein that gene is expressed in the host cells under the control of a conditional promoter, the activity of which depends on a function of the gene of interest to be evolved. Some aspects of this invention provide evolved products obtained from continuous evolution procedures described herein. Kits containing materials for continuous evolution are also provided.

The present invention relates to methods of producing microbubble drug conjugates, viral gene therapy microbubble drug conjugates, and disease-targeting microbubbles, for clinical and preclinical ultrasound-mediated therapeutic and diagnostic applications. It includes methods to produce viral vector gene therapy microbubble drug conjugates with antibody linkers conjugated to lipid shelled microbubbles that both bind to and neutralize viral vectors such that the viral gene therapy can transduce and effect permanent genetic changes only after ultrasound is used to disassociate the viral gene therapy from microbubbles at diseased regions of the body.

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.

The present disclosure relates to circular, non-viral DNA vectors, compositions including one or more of the disclosed vectors, and methods for delivering and / or expressing one or more therapeutic genes (e.g., proteins) in mammals, e.g., human patients. In some embodiments, the present disclosure is directed to circular, non-viral DNA vectors, such as circular non-viral DNA vectors including at least two inverted repeat sequences, where the at least two inverted repeat sequences are separated by a non-repeated nucleotide sequence which is not part of the at least two inverted repeat sequences. In some embodiments, the disclosed circular, non-viral DNA vectors do not include a “DD element.” In some embodiments, the disclosed circular, non-viral DNA vectors do not include a “DD element,” but include at least a portion of a bacterial origin of replication.

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

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).

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.

Described herein are compositions and methods for modifying eukaryotic cells, for example, to express a transgene of interest and / or to produce an expanded population of cells ex vivo. Using the compositions and methods of the disclosure, a population of eukaryotic cells, such as a population of pluripotent cells (e.g., CD34+ hematopoietic stem or progenitor cells) may be transduced to express a gene of interest by contacting the cells with a viral vector, such as a lentiviral vector, and a diblock copolymer, such as a diblock copolymer composed of a hydrophilic region and a hydrophobic region. For example, the diblock copolymer may be composed of polyoxyethylene (PEO) subunits and polyoxypropylene (PRO) subunits. Additionally, the compositions and methods described herein can be used to promote the proliferation or survival of a population of pluripotent cells (e.g., CD34+ hematopoietic stem or progenitor cells) ex vivo, for example, by contacting the cells with a diblock copolymer.

To provide recombinant adeno-associated viral vectors for treating Bietti Crystalline Dystrophy.SOLUTION: Provided are a recombinant adeno-associated vector comprising a codon-optimized sequence encoding CYP4 V2 linked to predetermine gene expression regulatory sequences, and its use in treating Bietti Crystalline Dystrophy (BCD).SELECTED DRAWING: None

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.

The invention discloses a CAR donor plasmid, a T cell as well as a preparation method and application of the CAR donor plasmid and the T cell, and belongs to the field of genetic engineering and immune cell therapy. An RNP compound and donor plasmid DNA are transferred into a T cell through electroporation, and a CAR expression unit is integrated into a T cell genome at a fixed point to prepare the CAR T cell. The donor plasmid DNA comprises a plasmid skeleton, a homologous arm sequence, an EF1 alpha core promoter, a CAR expression element and an SV40 poly A termination signal. The number of base pairs of the plasmid is 4544 bp, the toxicity of the plasmid to T cells after electroporation can be effectively reduced, and the T cell viability and the CAR integration efficiency are improved. Compared with dsDNA and ssDNA, the plasmid DNA is convenient to prepare and low in cost; therefore, the plasmid is taken as the donor template DNA, and the CRISPR / Cas9 technology is combined, so that the use of a virus vector can be avoided to improve the safety of the CAR T cell, and the production cost of the preparation of the CAR T cell can be effectively reduced.

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.

Provided herein are composition comprising a) a first recombinant adeno-associated viral (rAAV) vector genome comprising a first expression cassette comprising a promoter operably linked to nucleic acid sequence comprising a 5' portion of an otoferlin gene, wherein the first expression cassette is flanked by inverted terminal repeats (ITRs); and b) a second rAAV vector genome comprising a second expression cassette comprising a nucleic acid sequence comprising a 3' portion of an otoferlin gene, wherein the second expression cassette is flanked by ITRs, and wherein the composition can comprise about 4E10-9E13 vg / mL, optionally about about 4.1E10- 4.1E12 total vg or about 8.1E10-8.1E12 total vg and the use of these compositions to treat hearing loss in a subject.

The invention belongs to the field of biotechnology and biomedicine, and discloses an AAV system suitable for PFIC3 gene therapy and a preparation method. The system is composed of two adeno-associated virus vectors. The packaging plasmid of the adeno-associated virus vector comprises an auxiliary packaging plasmid pDP8.ape containing an AAV2Rep gene and an AAV8Cap gene, and a vector plasmid pAB288-Alb-hABCB4 for expressing an ABCB4 gene of human MDR3 protein, a self-cleavage protein P2A, a mouse albumin gene homologous arm sequence and an ITR sequence of AAV2, the packaging plasmid of the other adeno-associated virus vector comprises an auxiliary packaging plasmid pDP8.ape containing an AAV2Rep gene and an AAV8Cap gene, and a vector plasmid pX602-saCas9-gRNA for expressing a saCas9 protein and a sgRNA of a targeted mouse albumin genome.

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.