90 results about "Alphavirus" 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).

Provided herein are isolated polynucleotides encoding a polypeptide comprising an antigen protein fused to a signal sequence and a transmembrane domain, and optionally fused to a ferritin. Also provided herein are isolated polynucleotides encoding alphaviral non-structural proteins nsp1, nsp2, nsp3, and nsp4 and polypeptides comprising an antigen protein fused to a signal sequence and a transmembrane domain, and optionally fused to a ferritin. The antigen may be influenza. Polynucleotides, such as RNAs, can be used as vaccines against influenza infection.

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 discloses an mRNA (messenger ribonucleic acid) transcription skeleton vector and application thereof in preparation of a self-amplification type mRNA vaccine, and belongs to the technical field of veterinary biological products. According to the invention, alphavirus non-structural protein regions NSP2 and NSP3 of a self-amplification type mRNA skeleton are modified, a polyA tail is optimized, and a novel self-amplification type mRNA skeleton is constructed; the self-amplification type mRNA vaccine can improve the antigen expression efficiency, reduce the toxicity of non-structural protein to cells and improve the encapsulation efficiency and delivery efficiency by combining with the optimization of the components and proportion of a lipid nano delivery system, and meanwhile, the self-amplification type mRNA vaccine is wide in applicable pathogen antigen range and can be popularized to more animal epidemic diseases. The characteristics of high-efficiency expression, low-toxicity delivery and single-dose immunization are expected to renovate the immunization strategy of the existing animal vaccine, the epidemic prevention cost of the breeding industry is reduced, and the method has a wide industrial application prospect.

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 belongs to the technical field of mRNA vaccines, and particularly relates to a self-replicating mRNA vaccine as well as a preparation method and application thereof. The self-replicating mRNA is transcribed from an alphavirus skeleton vector, the alphavirus skeleton vector comprises gene sequences of alphavirus non-structural proteins nsP2, nsP3 and nsP4 and mutated nsP1, and cysteine at the 492nd position of the mutated nsP1 is mutated into serine. The self-replicating mRNA provided by the invention has higher expression quantity and longer expression time for the target gene. The self-replicating mRNA is used for expressing IMP3 and can be prepared into a vaccine with good prevention and treatment effects on IMP3 positive tumors. Therefore, the invention has a good application prospect in the development of medicines and vaccines.

Disclosed herein are alphavirus 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, 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 invention comprises compositions comprising at least two RNA replicons (self-amplifying RNA vector (saRNA or rRNA)) that can be replicated by a replicase of a self-replicating virus (e.g., a replicase of alphavirus origin). In the at least two replicons, at least one of the replicons optionally comprises an open reading frame encoding an RNA-dependent RNA polymerase or replicase, the RNA-dependent RNA polymerase or replicase being capable of replicating each of the at least two replicons. Furthermore, each replicon comprises an open reading frame encoding a different antigen of interest, such as a different antigen derived from the same or different pathogenic organism, such as glycoproteins and nucleoproteins of Ebola virus.

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 disclosure generally relates to methods for generating functional self-replicating RNA from non-functional positive single-stranded RNA (+ssRNA) viral genomes or srRNA, such as alphavirus genomes. More specifically, the methods relate to the assembly of multiple nucleic acid fragments to generate functional srRNA de novo. Also provided are compositions, nucleic acid constructs, vectors and recombinant cells comprising such functional srRNA. The present disclosure further discloses methods for inducing a pharmacodynamic effect in a subject, as well as methods for preventing and / or treating a health condition in a subject in need thereof.

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.

The present disclosure relates generally to the field of molecular virology, and in particular to nucleic acid molecules encoding modified alphavirus viral genomes or self-replicating RNA (srRNA) constructs, recombinant cells and pharmaceutical compositions containing the same, and the use of such nucleic acid molecules, recombinant cells, and compositions to produce desired products in cell culture or in vivo. Also provided are methods for inducing an immune response in a subject in need thereof, and methods for preventing and / or treating rabies virus infection.

The present invention embraces compositions comprising at least two RNA replicons (self-amplifying RNA vectors (saRNAs or rRNAs)) that can be replicated by a replicase of a self-replicating virus, e.g., a replicase of alphavirus origin. Of the at least two replicons, at least one of which optionally comprises an open reading frame encoding for the RNA-dependent RNA polymerase or replicase that is able to replicate each of the at least two replicons. Further, each replicon comprises an open reading frame encoding for different antigens of interest, e.g., different antigens derived from the same or from different pathogenic organisms, for example the glycoprotein and nucleoprotein of Ebola virus.

One aspect of the present invention provides: a vector including a gene encoding a non-structural alphavirus protein of and a gene encoding a target protein; a cell infected with the vector; a virus-like particle (VLP); and a vaccine composition comprising same. The vector is a single-vector system and can easily and conveniently produce VLP containing saRNA without a helper vector. The VLP and vaccine composition produced through the vector produce a sufficient amount of antibody from only a single administration, have excellent safety due to the absence of additional proliferation, can be administered to mucous membranes, and induces mucous membrane immunity, and thus exhibits a remarkably superior respiratory disease prevention or treatment effect compared to therapeutic agents for intramuscular administration.

The disclosure provides methods for an in vitro evolution technique to identify and characterize mutations in the non-structural genes of an alphavirus replicon that increase the strength and persistence of expression of the replicon genome. Also provided herein are in vivo methods for administering to an animal model a mutated alphavirus replicon that codes for a gene of experimental or therapeutic interest in the subgenome of the alphavirus replicon. The mutations identified herein improve the therapeutic potential of self-replicating RNA, which may have implications for cancer immunotherapy and beyond, e.g., for vaccination or gene therapy.

The present invention embraces a RNA replicon that can be replicated by a replicase of alphavirus origin and comprises an open reading frame encoding a reprogramming factor. Such RNA replicons are useful for expressing a reprogramming factor in a cell, in particular a somatic cell. Cells engineered to express such reprogramming factors are useful in cell transplantation therapies.

The present disclosure provides novel self-amplifying RNA (saRNA) constructs that demonstrate enhanced protein expression, prolonged durability, reduced immunogenicity, and the ability to express multiple therapeutic proteins homogeneously. The saRNA constructs comprise a 5' untranslated region (5'UTR), non-structural protein genes derived from alphaviruses, at least one gene of interest encoding a therapeutic protein, a 3' untranslated region (3'UTR), and one or more modified nucleosides. Also disclosed are dual construct systems comprising a first construct encoding non-structural proteins and a second construct encoding one or more genes of interest. Methods of producing and using the saRNA constructs for engineering cells, particularly immune cells, for treatment of various conditions including cancer, inflammatory conditions, and infectious diseases are provided. The saRNA constructs enable the generation of "armored" immune cells expressing multiple therapeutic proteins, thereby providing a multi-pronged approach to complex diseases.

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.

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 invention belongs to the technical field of mRNA vaccines, and particularly relates to a self-replicating mRNA vaccine as well as a preparation method and application thereof. The self-replicating mRNA is transcribed from an alphavirus skeleton vector, the alphavirus skeleton vector comprises gene sequences of alphavirus non-structural proteins nsP2, nsP3 and nsP4 and mutated nsP1, and cysteine at the 492nd position of the mutated nsP1 is mutated into serine. The self-replicating mRNA provided by the invention has higher expression quantity and longer expression time for the target gene. The self-replicating mRNA is used for expressing IMP3 and can be prepared into a vaccine with good prevention and treatment effects on IMP3 positive tumors. Therefore, the invention has a good application prospect in the development of medicines and vaccines.

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.

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.