46 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 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 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.

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

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.

The invention features modified alphavirus or flavivirus virus-like particles (VLPs). The invention provides methods, compositions, and kits featuring the modified VLPs. The invention also features methods for enhancing production of modified VLPs for use in the prevention or treatment of alphavirus and flavivirus-mediated diseases. The invention also provides methods for delivering agents to a cell using the modified VLPs.

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.

The application relates to the field of biotechnology, and particularly discloses application of an autophagy inhibiting small molecule compound in preparation of a virus infection inhibiting product. The application finds that a specific autophagy inhibiting small molecule compound can inhibit infection of various viruses, and further proposes application of the compound in preparation of a virus infection inhibiting product, the compound being one or a combination of substances as shown in formulae I-IV: formula I; formula II; formula III; and formula IV; the viruses including one or a combination of influenza viruses, coronaviruses, alphaviruses or vesicular stomatitis viruses. The compound of the application can effectively inhibit infection of various viruses, and provides a new broad-spectrum antiviral method, which can be used for simultaneously preventing and / or treating diseases caused by various viruses.

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.

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.

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 invention provides an optimization method for enhancing self-amplification RNA (Ribonucleic Acid) expression and enhanced self-amplification RNA, and particularly provides the optimization method for enhancing self-amplification RNA expression, the optimization is codon optimization, a codon optimization region is an alphavirus non-structural protein sequence specific region of the self-amplification RNA, alphavirus non-structural protein is nsP1234, and the alphavirus non-structural protein is nsP1234. The invention also provides a preparation method of the enhanced self-amplification RNA, the enhanced self-amplification RNA and a plasmid. According to the invention, the codon sequences of partial regions of the non-structural proteins are optimized through design and construction, so that the expression efficiency of the self-amplification RNA target gene is improved.

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.

Salmonid alphavirus (SAV) is an important pathogen affecting the aquaculture of Salmonid fish. Vaccines based on DNA plasmids expressing a SAV antigen have been described. However these are difficult to prepare at large scale and at the desired quality level. Also, they are commonly administered at relatively high amounts of plasmid per animal dose. This makes such DNA vaccines less affordable for this market. The invention discloses an improved plasmid that allows effective use as a DNA vaccine against SAV, but at a much reduced amount of DNA per dose. The plasmid contains a gene encoding a bacterial enzyme: Fab.