27 results about "Alphavirus" patented technology

A provided self-replicating mRNA is transcribed from an alphavirus backbone vector. The alphavirus backbone vector comprises gene sequences of alphavirus non-structural proteins nsP2, nsP3, nsP4, and mutated nsP1. A cysteine at position 492 of the mutated nsP1 is mutated into serine. The self-replicating mRNA has a higher expression level and a longer expression time for a target gene. The self-replicating mRNA is used for expressing IMP3, and can be prepared into a vaccine having good preventive and therapeutic effects on IMP3-positive tumors. Therefore, the present invention has good application prospects in drug and vaccine development.

The present invention relates to a composition comprising a self-amplifying RNA (saRNA) encoding at least one polypeptide of infectious laryngotracheitis virus (ILTV; Gallid alphaherpesvirus 1, GaHV-1), a polypeptide variant of ILTV, or an immunogenic fragment or epitope thereof, and a pharmaceutically acceptable excipient comprising lipid inorganic nanoparticles (LION).More specifically, the sRNA encodes at least one laryngotracheitis virus polypeptide, an ILTV polypeptide variant, or an immunogenic fragment or epitope thereof, said sRNA comprising a first nucleic acid sequence including nsP1, nsP2, nsP3 and nsP4 which encode non-structural alphavirus proteins, a second nucleic acid sequence encoding at least one ILTV polypeptide, an ILTV polypeptide variant, an immunogenic fragment or an epitope thereof, and also comprising a 5' cap, a 5' UTR upstream of the first nucleic acid sequence, a 26S promoter upstream of the second nucleic acid sequence, a 3' UTR and a poly A tail.

The present disclosure relates to a novel system for the generation and use of hybrid alpha-pseudoviruses against ribose viruses. A hybrid ribose virus-alpha-pseudovirus (HRAP) presents a novel particle having an RNA genome derived from an alphavirus and a structural protein of a virus in the ribose virus field. The HRAP particle is formed by assembling structural proteins crossing different riboviridae and can be used for vaccine development, antiviral drug screening, neutralization test, treatment or immune response starting and the like.

The present disclosure provides neutralising human antibodies that binds to an alphavirus. The antibodies are raised against the chikungunya (CHIKV) virus, and show cross-neutralisation and in vivo protection of other alphaviruses.

To provide a CRISPR gene delivery system that ensures robust expression of CRISPR proteins and avoids the risk of genomic integration. [Solution] A synthetic, non-infectious, self-replicating RNA vector encoding a CRISPR protein is provided. Each self-replicating RNA vector contains sequences encoding multiple non-structural replication complex proteins derived from alphaviruses, and sequences encoding a CRISPR protein. A method for genome editing is also provided, which involves introducing a synthetic self-replicating RNA vector into a cell along with at least one corresponding guide RNA.

The invention provides a self-replicating RNA (Ribonucleic Acid) construct as well as a preparation method and application thereof, and in particular relates to a self-replicating RNA construct derived from an alphavirus replicon as well as a preparation method and application thereof. According to the present invention, the expression of the target gene is enhanced through the specific sequence mutation, and the cytotoxicity of the self-replicating RNA construct is effectively reduced.

Provided are a self-replicating RNA construct, and a preparation method therefor and the use thereof. More specifically, the present invention relates to a self-replicating RNA construct derived from an alphavirus replicon, and a preparation method therefor and the use thereof. The cytotoxicity of the self-replicating RNA construct is effectively reduced by enhancing the expression of a target gene by means of a specific sequence mutation.

The present invention provides new canine Influenza H3N2 vaccines, including multivalent vaccines. The present invention provides an alphavirus RNA replicon particle that encodes a Canine Influenza (CIV) H3N2 hemagglutinin (HA) antigen. The present invention further provides methods of making and using the vaccines.

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 relates to self-amplifying RNA (saRNA) vaccines against infectious laryngotracheitis (ILT) that provide safe and effective prophylactic and therapeutic immune responses and improve the symptoms of the disease.In particular, the invention relates to sRNAs encoding at least one laryngotracheitis virus polypeptide, an ILTV polypeptide variant, or an immunogenic fragment or epitope thereof, said sRNA comprising a first nucleic acid sequence including nsP1, nsP2, nsP3, and nsP4 encoding non-structural alphavirus proteins, a second nucleic acid sequence encoding at least one ILTV polypeptide including gB or gBdel, linked to gD by a nucleic acid sequence encoding at least one protein-binding site or at least one cleavage site for an endogenous or exogenous protease such as a 6k sequence, and also comprising a 5' cap, a 5' UTR upstream of the first nucleic acid sequence, a 26S promoter upstream of the second nucleic acid sequence, a 3' UTR, and a poly tail HAS.The sRNA according to the present invention allows, when incorporated into a cell, the expression of at least one ILTV polypeptide, an ILTV polypeptide variant, or an immunogenic fragment or an epitope of one of them.

Self-amplifying RNA (saRNA) vectors are disclosed. The described saRNA vectors are adapted from genotypically diverse alphaviruses. The described saRNA vectors are used in the expression of heterologous genes. Efficacious saRNA vaccines and therapies may be produced from such saRNA vectors.

The present invention relates to self-amplifying RNA (saRNA) vaccines against infectious laryngotracheitis (ILT) that provide safe and effective prophylactic and therapeutic immune responses and improve the symptoms of the disease. In particular, the invention relates to sRNAs encoding at least one laryngotracheitis virus polypeptide, an ILTV polypeptide variant, or an immunogenic fragment or epitope thereof, said sRNA comprising a first nucleic acid sequence comprising nsP1, nsP2, nsP3 and nsP4 which encode non-structural alphavirus proteins, a second nucleic acid sequence encoding at least one ILTV polypeptide, an ILTV polypeptide variant, an immunogenic fragment or an epitope thereof, and also comprising a 5' cap, a 5' UTR upstream of the first nucleic acid sequence, a 26S promoter upstream of the second nucleic acid sequence, a 3' UTR and a poly A tail.The sRNA according to the present invention allows, when incorporated into a cell, the expression of at least one ILTV polypeptide, an ILTV polypeptide variant, or an immunogenic fragment or an epitope of one of them.

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 relates to self-amplifying RNA (saRNA) vaccines against infectious laryngotracheitis (ITL) that provide safe and effective prophylactic and therapeutic immune responses and improve the symptoms of the disease. In particular, the invention relates to sRNAs encoding at least one laryngotracheitis virus polypeptide, an ILTV polypeptide variant, or an immunogenic fragment or epitope thereof, said sRNA comprising a first nucleic acid sequence comprising nsP1, nsP2, nsP3 and nsP4 which encode non-structural alphavirus proteins, a second nucleic acid sequence encoding at least one ILTV polypeptide comprising gB or gBdel, gD, gI and / or gE and gC, and also comprising a 5' cap, a 5' UTR upstream of the first nucleic acid sequence, a 26S promoter upstream of the second nucleic acid sequence, a 3' UTR and a poly A tail.The sRNA according to the present invention allows, when incorporated into a cell, the expression of at least one ILTV polypeptide, an ILTV polypeptide variant, or an immunogenic fragment or an epitope of one of them.

The invention features compositions and methods for the prevention or treatment of one or more strains of Chikungunya virus, as well as other alphavirus-mediated diseases.

Compounds, methods, and compositions for treating or preventing viral infections using nucleoside compounds. The nucleoside compounds have increased antiviral activity potential with the result of inhibiting at least one of flaviviruses, herpesviruses, polyomaviruses, alphaviruses, enteroviruses, filoviruses matonaviruses, phenuiviruses, Hepatitis B virus, and / or coronaviruses.

A method for constructing a saRNA microvesicle delivery system includes the following steps: (1) designing a saRNA expression vector 1 and a membrane protein expression vector 2; and (2) co-transfecting the expression vector 1 and the expression vector 2 into a host cell; and (3) culturing the host cell, and isolating microvesicles containing a saRNA, the saRNA containing a target gene sequence, a replicon in the saRNA expression vector being an alphavirus replicon, and the microvesicles not containing capsid protein. The system can efficiently deliver the saRNA to cells or in vivo to realize the expression of a target protein. On this basis, different elements in the delivery system can be further transformed to develop a high-efficiency low-immunogenicity modular platform aiming at different diseases and different targets. The delivery system may supplement the toolbox of existing viral and lipid nanoparticle delivery vectors and has good application prospects.

To provide improved cytokine immunotherapy for cancer and / or inflammatory diseases. [Solution] This disclosure provides a novel immunologically active alphavirus repliconvector containing nucleic acids encoding alphavirus non-structural proteins nsp1-4 and cytokine proteins / polypeptides. The alphavirus repliconvector of this disclosure is useful for the treatment of cancer and / or inflammatory diseases.

This disclosure belongs to the field of biotechnology and specifically relates to a method for constructing an saRNA microvesicle delivery system. The method comprises the steps of (1) designing an saRNA expression vector 1 and a membrane protein expression vector 2, (2) co-transfecting an expression vector 1 and an expression vector 2 into a host cell, and (3) culturing the host cell and isolating microvesicles containing saRNA, wherein the saRNA contains a target gene sequence, the replicon of the saRNA expression vector is an alphavirus replicon, and the microvesicles do not contain a capsid protein. This system can efficiently deliver saRNA into cells or the body and achieve the expression of a target protein. Furthermore, by improving different elements of this delivery system, a highly efficient and less immunogenic modular platform for different diseases and targets can be developed. This delivery system has the potential to complement existing viral and lipid nanoparticle delivery vector toolkits and shows promising future application potential.

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).

Relates to an alphavirus RNA replicase coding sequence, an optimized self-amplification nucleic acid molecule, a pharmaceutical composition and application, and the optimized self-amplification nucleic acid molecule is a self-amplification nucleic acid molecule containing the alphavirus RNA replicase coding sequence, a tissue-specific self-amplification nucleic acid molecule or an improved self-amplification mRNA containing a mutated replicase. The mutated replicase comprises a mutated macro domain. The invention also relates to a preparation method of the self-amplification nucleic acid molecule.

The present invention relates to self-amplifying RNA (saRNA) vaccines against infectious laryngotracheitis (ILT) that provide safe and effective prophylactic and therapeutic immune responses and improve the symptoms of the disease.In particular, the invention relates to sRNAs encoding at least one laryngotracheitis virus polypeptide, an ILTV polypeptide variant, or an immunogenic fragment or epitope thereof, said sRNA comprising a first nucleic acid sequence including nsP1, nsP2, nsP3, and nsP4 encoding non-structural alphavirus proteins, a second nucleic acid sequence encoding at least one ILTV polypeptide including gB, gBdel, gD, or gE linked to gI by a nucleic acid sequence encoding at least one protein-binding site or at least one cleavage site for an endogenous or exogenous protease such as a 6k sequence, and also comprising a 5' cap, a 5' UTR upstream of the first nucleic acid sequence, a 26S promoter upstream of the second nucleic acid sequence, and a 3' UTR. and a poly A tail.The sRNA according to the present invention allows, when incorporated into a cell, the expression of at least one ILTV polypeptide, an ILTV polypeptide variant, or an immunogenic fragment or an epitope of one of them.

The present invention provides an RNA replicon useful for administering a heterologous protein or peptide to a mammal to elicit a reduced or no immune response from the mammal. The RNA replicon comprises an RNA sequence encoding the heterologous protein or peptide, an RNA sequence encoding the nonstructural proteins nsP1, nsP2, and nsP4 of a New World alphavirus, and an RNA sequence encoding the macrodomain, central domain, and hypervariable domain of the alphavirus nsP3 protein. The encoded hypervariable domain may have an amino acid sequence derived from an Old World alphavirus nsP3 hypervariable domain, or may have an amino acid sequence derived from a portion of the New World alphavirus nsP3 hypervariable domain and another portion derived from an Old World alphavirus nsP3 hypervariable domain.

The present invention relates to self-amplifying RNA (saRNA) vaccines against infectious laryngotracheitis (ILT) that provide safe and effective prophylactic and therapeutic immune responses and improve the symptoms of the disease.In particular, the invention relates to sRNAs encoding at least one laryngotracheitis virus polypeptide, an ILTV polypeptide variant, or an immunogenic fragment or epitope thereof, said sRNA comprising a first nucleic acid sequence including nsP1, nsP2, nsP3, and nsP4 encoding non-structural alphavirus proteins, a second nucleic acid sequence encoding at least one ILTV polypeptide including gB, gBdel, or gD, linked to gE by a nucleic acid sequence encoding at least one protein-binding site or at least one cleavage site for an endogenous or exogenous protease such as a 6k sequence, and also comprising a 5' cap, a 5' UTR upstream of the first nucleic acid sequence, a 26S promoter upstream of the second nucleic acid sequence, a 3' UTR, and a Poly queue A.The sRNA according to the present invention allows, when incorporated into a cell, the expression of at least one ILTV polypeptide, an ILTV polypeptide variant, or an immunogenic fragment or an epitope of one of them.

This article provides information on mutant reverse tetracycline transactivator (rtTA) protein and engineered nucleic acids (e.g., viral vectors, including lentiviral vectors, adenovirus vectors, AAV vectors, herpesvirus vectors, and retroviral vectors; and non-viral vectors, including RNA and plasmid DNA) encoding mutant rtTA, which can be used for, for example, regulating gene expression, inducing cell reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, treating diseases (e.g., acute injury, neurodegenerative diseases, chronic diseases, proliferative diseases, cardiovascular diseases, genetic diseases, inflammatory diseases, autoimmune diseases, neurological diseases, hematological diseases, pain conditions, mental disorders, metabolic disorders, cancer, aging, age-related diseases, and diseases affecting any tissue in a subject), or any combination thereof. This article also provides recombinant viruses comprising engineered nucleic acids (e.g., lentiviruses, adenoviruses, alphaviruses, vaccinia viruses, retroviruses, herpesviruses, or AAVs), and methods for modulating (e.g., inhibiting or inducing) cell reprogramming, tissue repair, tissue regeneration, or any combination thereof by applying engineered nucleic acids or recombinant viruses comprising them to cells, tissues, or subjects (e.g., cells or tissues of subjects with a condition, said condition including any disease (e.g., eye disease), aging, neurodegenerative diseases, cancer, and age-related diseases), said application including the application of a mutant rtTA and an inducible nucleic acid encoding a transgene (e.g., engineered nucleic acid, including an expression vector).

This paper discusses an alphavirus RNA replicase-encoding sequence, an optimized self-amplifying nucleic acid molecule, a pharmaceutical composition, and a use thereof. The optimized self-amplifying nucleic acid molecule comprises either a self-amplifying nucleic acid molecule containing the alphavirus RNA replicase-encoding sequence, a tissue-specific self-amplifying nucleic acid molecule, or an enhanced self-amplifying mRNA with a mutated replicase, wherein the mutated replicase includes a mutated macrodomain. A manufacturing process for the self-amplifying nucleic acid molecule is also discussed.