66 results about "Alphavirus" patented technology

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).

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.

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.

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 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.

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.

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 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.

To provide RNA replicons useful for administering a heterologous protein or peptide into a mammal and eliciting a reduced immune response or no immune response from the mammal.SOLUTION: The RNA replicon comprises RNA sequences encoding a heterologous protein or peptide, New World alphavirus nonstructural proteins nsP1, nsP2, and nsP4, and an alphavirus nsP3 protein macro domain, central domain, and hypervariable domain. 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 a New World alphavirus nsP3 hypervariable domain and another portion derived from an Old World alphavirus nsP3 hypervariable domain.SELECTED DRAWING: Figure 2

The invention relates to a recombinant SFV E1 protein, a recombinant alphavirus vector system and a method for packaging alphavirus by using the E1 protein and the alphavirus vector system.

The present invention relates to systems and methods suitable for high-level protein production. In particular, a system comprising two separate RNA molecules is foreseen, each comprising a nucleotide sequence derived from an alphavirus: one RNA molecule comprises a RNA construct for expressing alphavirus replicase, and one RNA molecule comprises a RNA replicon that can be replicated by the replicase in trans. The system of the present invention enables expression of a protein of interest in a cell or organism, but is not associated with undesired virus-particle formation. The present invention is suitable for efficiently and safely producing a protein of interest in a target organism. Respective methods of protein production in vitro and in vivo as well as medical uses are provided herein. The present invention also provides DNA encoding the RNA molecules of the invention, and cells comprising the RNA molecules of the invention.

Genetically engineered alphavirus constructs (e.g., Mayaro virus) attenuated in normal human by increasing CpG dinucleotides frequency and its oncolytic potential against lung and pancreatic cancer. The modified virus may also be used as a live attenuated vaccine against MAYV.

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 are high affinity anti-alphavirus antibody or alphavirus-binding fragment thereof, as well as methods of use and devices employing such antibodies and / or fragments.

An iRNA and / or iDNA vaccine system and / or platform are described for eliciting an immune response against one or more pathogens. Also described, are methods of making and using the iRNA and / or iDNA vaccine system and / or platform.

The present invention generally relates to systems and methods suitable for high-level protein production. While one or more elements of the present invention are derived from an alphavirus, the present invention does not require propagation of virus particles. In particular, a system comprising two separate RNA molecules is foreseen, each comprising a nucleotide sequence derived from an alphavirus: one RNA molecule comprises a RNA construct for expressing alphavirus replicase, and one RNA molecule comprises a RNA replicon that can be replicated by the replicase in trans. The RNA construct for expressing alphavirus replicase comprises a 5′-cap. It was surprisingly found that the 5′-cap is suitable for efficiently driving expression of a transgene from the replicon in trans. The system of the present invention enables expression of a protein of interest in a cell or organism, but is not associated with undesired virus-particle formation. Therefore, the present invention is suitable for efficiently and safely producing a protein of interest, e.g. a therapeutic protein or an antigenic protein, such as a vaccine, in a target organism. Respective methods of protein production in vitro and in vivo as well as medical uses are provided herein. The present invention also provides DNA encoding the RNA molecules of the invention, and cells comprising the RNA molecules of the invention.