459 results about "Recombinant virus" patented technology

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 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.

The invention provides application of a porcine parainfluenza virus type 5 as an expression vector, and belongs to the technical field of biological vaccines. According to the invention, a PIV5 strain separated from diarrhea pigs in Jiangsu Province in China is utilized to construct PIV5 virus infectious clone. The eGFP gene is inserted into a PIV5 infectious cloned virus genome, the recombinant PIV5 virus capable of expressing the green fluorescent protein is successfully rescued, and when the eGFP gene is inserted into a P / M gene spacer region, the expression quantity is the highest, which indicates that an exogenous gene expression cassette can influence the expression level of an exogenous gene, and the P / M gene spacer region is the optimal site for inserting the exogenous gene, so that the recombinant PIV5 virus can be successfully rescued. And a solid foundation is laid for developing a vector vaccine by utilizing the swine PIV5. The porcine parainfluenza virus type 5 can be used as an expression vector to express foreign proteins, can also be used for preparing oral vaccines, and can relieve the stress reaction of pigs in the immune process.

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 belongs to the technical field of biology, and discloses a recombinant turkey herpesvirus co-expressing an avian influenza H9 gene and an avian adenovirus 4 type Fiber-2 gene, the H9 gene containing a promoter and a terminator is inserted between an HVT053 site and an HVT054 site of the turkey herpesvirus, the Fiber-2 gene containing a promoter and a terminator is inserted between an HVT087 site and an HVT088 site of the turkey herpesvirus, and the recombinant turkey herpesvirus co-expressing the avian influenza H9 gene and the avian adenovirus 4 type Fiber-2 gene is obtained. The recombinant virus is obtained. The recombinant turkey herpesvirus can stably co-express the H9N2 subtype avian influenza virus H9 protein and the fowl adenovirus 4 type Fiber-2 protein, has very excellent immune performance, and effectively improves the immune effect of the recombinant virus of the traditional fowl adenovirus Fiber-2 gene; compared with the recombinant herpesvirus of turkey which singly expresses any one of the H9N2 subtype avian influenza virus H9 protein and the fowl adenovirus 4 type Fiber-2 protein, the recombinant herpesvirus of turkey has the advantage that the performance of the recombinant herpesvirus of turkey is not weakened. Meanwhile, the invention also provides application and a vaccine of the recombinant herpesvirus of turkeys.

The invention relates to the field of aquaculture, in particular to a preparation method and application of a larimichthys crocea iridovirus recombinant live vector vaccine. According to the invention, replication-deficient type 5 adenovirus is selected as a target gene expression vector, a recombinant adenovirus vector comprising main capsid protein of iridovirus is constructed, recombinant virus is obtained, and the safe and effective large yellow croaker iridovirus disease recombinant live vector vaccine is created. According to the vaccine, the larimichthys crocea is immunized in a soaking or bait feeding mode, the CPM of the larimichthys crocea immunized by the vaccine is 12.0%, and the CPM of the fish without being immunized by the vaccine is 62.0%. In addition, the RPS of the inoculated fish and the RPS of the empty carrier control group fish are 80.65% and 9.68% respectively. The method is at a leading level in the field of pseudosciaena crocea biomedicine at present, and creativity is remarkable.

The invention discloses a chimeric PEDV (porcine epidemic diarrhea virus) infectious clone plasmid, a PEDV chimeric virus as well as a construction method and application thereof. According to the invention, a PEDV genome is used as a skeleton for the first time, the chimeric virus for expressing the extracellular domain of the TGEV S protein is successfully rescued, and it is found that the TCID50 of the chimeric virus for expressing the extracellular domain of the TGEV S protein can be increased by 6.2 times compared with that of the chimeric PEDV for expressing the TGEV S protein. The recombinant virus is used as an inactivated vaccine for immunizing mice, so that the immunogenicity of TGEV S protein can be greatly improved, a body is stimulated to generate a higher-level neutralizing antibody aiming at TGEV, and the titer of the neutralizing antibody aiming at TGEV is improved by 16.8 times. Therefore, more possibilities are provided for modification of viral genomes, a novel method for improving immunogenicity of the TGEV inactivated vaccine is invented, and a basis is provided for research and development of the TGEV vaccine.

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).

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 present disclosure provides recombinant adeno-associated virus (AAV) virions with altered capsid protein, where the recombinant AAV (rAAV) virions exhibit greater ability to cross barriers between intravitreal fluid and retinal cells, and thus greater infectivity of a retinal cell compared to wild-type AAV, and where the rAAV virions comprise a heterologous nucleic acid. The present disclosure provides methods of delivering a gene product to a retinal cell in an individual.

The invention discloses an HSV-1 replication-deficient recombinant virus vector and an application of the HSV-1 replication-deficient recombinant virus vector. Specifically, the method comprises the following steps: performing gene editing on a specific genome segment in an HSV-1 genome to obtain an HSV-1 replication-defective recombinant virus vector; wherein compared with the existing HSV-1 replication-deficient recombinant virus vector, the HSV-1 replication-deficient recombinant virus vector can express an exogenous gene more efficiently, and the HSV-1 replication-deficient recombinant virus vector, as an excellent delivery vector, can effectively deliver the exogenous gene into the body of a subject to achieve a treatment effect.

The invention discloses a PDCoV JS2021-LX strain NS6 gene deletion recombinant virus and a construction method thereof, on the basis of PDCoV JS2021-LX strain infectious clone successfully constructed by a BAC system, the upstream and downstream of the NS6 gene are cut by adopting a CRISPR / Cas9 technology, then the original NS6 gene segment is replaced by green fluorescent protein EGFP through a homologous recombination mode, an NS6 gene deletion recombinant plasmid is obtained, and the NS6 gene deletion recombinant virus is constructed. And after the LLC-PK1 cell is transfected, the recombinant virus without the NS6 protein is rescued. The recombinant virus with the PDCoV NS6 gene deleted is successfully rescued, the virus replication level of the recombinant virus and the virus is rescued through in-vivo and in-vitro evaluation, and pig experiment results show that the pathogenicity of the recombinant virus is reduced, and the recombinant virus has the potential of serving as a candidate strain of an attenuated live vaccine.

The invention discloses an HSV-1 replication-deficient recombinant virus vector and an application of the HSV-1 replication-deficient recombinant virus vector. Specifically, the method comprises the following steps: performing gene editing on a specific genome segment in an HSV-1 genome to obtain an HSV-1 replication-defective recombinant virus vector; wherein compared with the existing HSV-1 replication-deficient recombinant virus vector, the HSV-1 replication-deficient recombinant virus vector can express an exogenous gene more efficiently, and the HSV-1 replication-deficient recombinant virus vector, as an excellent delivery vector, can play a role in supplementing normal keratin.

The present invention relates to treatment of COVID-19 and methods thereof. A vaccine composition for inducing immunity against coronavirus in a subject comprises a recombinant nucleic acid encoding an N-ETSD, which is a modified nucleocapsid protein comprising an endosomal targeting sequence, and / or a recombinant nucleic acid encoding an S-fusion, which is a modified spike protein with improved surface expression. The vaccines can be formulated as recombinant nucleic acids, recombinant yeasts, and / or recombinant viruses, such as adenoviruses, and can be administered via injection and / or mucosal delivery.

Provided are an AAV virus vector expressing an anti-VEGF fusion protein or antibody and a use of the AAV virus vector. Specifically, provided are a recombinant AAV virus vector comprising a nucleotide sequence encoding an anti-VEGF fusion protein or antibody, and a use of the recombinant AAV virus vector. The recombinant AAV virus exhibits an excellent infection effect in human cells and mouse cells, is stably and abundantly expressed within cells, and can effectively inhibit intraocular VEGF, and reduce leakage and angiogenesis caused by laser damage. Moreover, the AAV virus can be utilized to deliver an anti-VEGF fusion protein or an anti-VEGF antibody in the administration manner of subretinal injection, so that the objective of a single injection with long-term effectiveness is achieved; thus, the AAV virus can be used to prepare a drug for treating VEGF related diseases, and has broad market prospects.

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 invention belongs to the technical field of biological medicine, and particularly relates to construction of a rotavirus reverse genetic system and application of the rotavirus reverse genetic system in rescue of NMTL porcine rotavirus strains. Reverse genetic operating systems utilized by rescue work aiming at rotaviruses of different genotypes are obviously different. Aiming at the G9P [23] genotype porcine rotavirus strain, 11 gene segments of porcine rotavirus are recombined to a pOK-T7 vector to obtain 10 porcine rotavirus infectious recombinant plasmids, genes of encoding viruses NSP2 and NSP5 are put into one plasmid to obtain a pOK-T7-NSP2 / 5 plasmid, and the plasmid is used for preparing the porcine rotavirus infectious recombinant plasmids. And finally, a reverse genetic system based on 10 porcine rotavirus infectious recombinant plasmids is formed. By applying the system, the G9P [23] genotype porcine rotavirus NMTL strain can be successfully rescued, and the rNMTL porcine rotavirus recombinant strain is obtained.

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 provides a rabies virus inactivated vaccine and a preparation method thereof, and belongs to the technical field of biological medicines. The invention provides a rabies virus inactivated vaccine. The rabies virus inactivated vaccine comprises an adjuvant and an inactivated VSV-rabies recombinant virus, the inactivated VSV-rabies recombinant virus is obtained by carrying out inactivation on a VSV-rabies recombinant live virus; the VSV-rabies recombinant live virus is prepared by replacing envelope protein G of vesicular stomatitis virus with G protein of rabies virus. The inactivated rabies virus vaccine is good in safety and high in induced antibody level, the immune effect of the inactivated rabies virus vaccine is equivalent to that of a live virus vector vaccine, and the inactivated rabies virus vaccine has a certain application value in the aspect of preventing and controlling rabies.

The invention discloses an ILTV gD protein antigen epitope expression cassette, a recombinant virus and application, and relates to the field of gene and protein engineering. The ILTV gD protein antigen epitope expression cassette provided by the invention comprises T and B cell epitopes of gD protein derived from an infectious laryngotracheitis virus WG strain. The recombinant virus rH120-gD-T / B is obtained by replacing a 5ab gene of an infectious bronchitis virus H120 strain with a gene for coding an ILTV gD protein antigen epitope expression cassette. The recombinant virus has good genetic stability, can be used for developing a safe and effective IB-ILT bivalent live vector vaccine, and solves the problem of poor stability of the current recombinant IBV.

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 present invention relates to a method for producing higher titers and / or a higher quality of recombinant viruses and / or less or reduced impurities in virus like particle (VLP) production in respective production processes in mammalian cell lines, the method comprising the step of supplementing a suitable mammalian cell line culture media with at least one intermediate substrate of the tricarboxylic acid (TCA) cycle and optionally supplementing the suitable mammalian cell line culture media with further additives and / or further adjusting the conditions of the mammalian cell line culture media. Furthermore, the present invention relates to the balanced suitable mammalian cell line culture media and the use of this balanced suitable mammalian cell line culture media for producing higher titers and / or a higher quality of recombinant viruses and / or less or reduced impurities in virus like particle (VLP) production in respective production processes for producing higher titers and / or quality of recombinant viruses.

The invention relates to the technical field of biology, in particular to a chimeric antigen receptor of a specific targeting tumor non-classical HLA molecule, polynucleotide, an expression vector, a recombinant virus, a recombinant cell, a composition and pharmaceutical application. An extracellular domain of the chimeric antigen receptor specifically combined with the HLA-G in a targeted manner is an antigen binding structural domain of an ILT2 receptor, and compared with a CAR modified immune cell with an antigen binding region of an antibody as an extracellular domain, the HLA-G targeted immune response cell provided by the invention can recognize numerous tumor cells in a broad-spectrum manner on one hand, so that the HLA-G targeted immune response cell can be used for preparing an HLA-G targeted immune response cell; the killing efficiency and accuracy of various tumor cells are greatly improved; and on the other hand, the extracellular domain is an antigen binding domain of an ILT2 receptor, and the binding domain is a binding domain of a natural receptor, so that compared with an artificially synthesized antibody, the antigen binding domain is safe and reliable, and can truly reflect the target binding capacity in a natural state.

An MYL4 gene, a protein encoded thereby, a recombinant plasmid expressing same, a recombinant virus expressing same or a transgenic cell expressing same in the preparation of a drug for treating or preventing atrial diseases; the MYL4 gene has an NCBI number of NM_002476.2.The expression of the MYL4 gene and the protein expressed thereby is increased, so that atrial cardiomyopathy caused by multiple factors is improved, atrial structural remodeling and electrical remodeling are reduced, and atrial fibrosis, apoptosis and electrical conduction abnormality are reduced.

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 application belongs to the technical field of biotechnology, and particularly relates to a porcine epidemic diarrhea virus recombinant strain, a construction method and application. The S gene sequence of the existing epidemic porcine epidemic diarrhea virus PEDV CH / SX / 2016 strain is replaced by the S2015 gene sequence shown in SEQ ID NO. 1 to construct a PEDV CH / SX / 2016 strain infectious clone. A porcine epidemic diarrhea virus recombinant strain rCH / SX / 2016-S 2015 is successfully rescued by transfecting cells with a plasmid containing the infectious cDNA shown in SEQ ID NO. 4. The problem that the original strain cannot be successfully rescued by reverse genetics engineering is solved, and the recombinant virus strain rCH / SX / 2016-S 2015 has an activity comparable to that of the original strain, and can be used for preparing a PEDV diagnostic reagent and / or vaccine.

Nucleotide compositions, recombinant vectors, and recombinant viral genomes are disclosed that include a modified horseradish peroxidase (HRP) gene sequence, as well as recombinant viruses that have the modified HRP gene sequence incorporated into the viral genome thereof. The recombinant viruses are utilized in an HRP-based assay to analyze the neutralization potential of candidate antiviral agents, such as antiviral antibodies.

The invention provides a recombinant herpes simplex virus and a herpes simplex virus modification method. The herpes simplex virus modification method comprises the step of replacing an ICP4 protein coding gene in a herpes simplex virus genome containing an infected cell protein 4 (ICP4) gene with an hTERTp-fluorescent protein expression cassette. The expression cassette comprises an hTERTp promoter and a fluorescent protein coding sequence controlled by the hTERTp promoter, and the transcription direction is opposite to that of an ICP4 promoter in a genome. The hTERTp-fluorescent protein expression cassette in the recombinant virus obtained by the method disclosed by the invention can be normally expressed in response to telomerase activity. Therefore, the recombinant virus is capable of expressing a fluorescent protein, such as mBaoJin, in a cell having human telomerase activity. Cells infected by the virus can be identified through fluorescence signals, and the higher the telomerase activity is, the stronger the fluorescence intensity is. The virus has wide application value in research of tumor action mechanisms and stem cell action mechanisms, health assessment, screening of tumor drugs, research and development of diagnostic reagents and establishment of animal models.

The invention discloses akabane disease virus recombinant virus-like particles and a preparation method thereof, and belongs to the technical field of biology. The akabane disease virus recombinant virus-like particles are obtained by recombinant expression of structural protein Gn and structural protein Gc of akabane disease virus in an insect cell-baculovirus expression system and self-assembly; the amino acid sequence of the structural protein Gn is as shown in SEQ ID NO. 1; the amino acid sequence of the structural protein Gc is as shown in SEQ ID NO. 2. According to the invention, genes of coding structural proteins Gn and Gc are optimized according to codon preference of insect cells, and AKAV virus-like particles with higher safety are successfully prepared through a baculovirus-insect cell expression system. The AKAV virus-like particle provided by the invention has application potential in various fields of AKAV vaccines, immunotherapy and the like, and provides technical reserve for biological safety monitoring.

The present invention relates to the prevention or mitigation of adverse reactions associated with gene therapy, such as the formation of anti-drug antibodies. In particular, the present invention relates to the use of tyrosine kinase inhibitors, such as dasatinib, to prevent or ameliorate such side effects.