Disclosed are recombinant oncolytic viruses that express one or more reovirus fusion-associated small transmembrane FAST) proteins and uses thereof. The oncolytic activity of the recombinant oncolytic viruses expressing FAST proteins can be used to treat primary and metastatic cancers, especially from breast and colon cancers.

An isolated polypeptide comprising an amino acid sequence corresponding to the amino acid residues forming a full or partial -helical domain, the hinge domain, the -triple spiral domain and a full or partial globular head domain of an avian reovirus sigma C protein, and lacking the amino acid sequence that is N-terminal to said -helical domain is provided. Furthermore, a vaccine comprising, or a viral vector expressing, at least one of the isolated polypeptides of the present invention is provided.

Provided nucleic acid-based expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, within a target cell, including a target cell that is associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell. Also provided are formulations and systems, including fusogenic lipid nanoparticle (LNP) formulations and systems, for the delivery of nucleic acid-based expression constructs as well as methods for making and using such nucleic acid-based expression constructs, formulations, and systems for reducing, preventing, and/or eliminating the growth and/or survival of a cell, such as a senescent cell and/or a cancer cell, which is associated with aging, disease, or other condition as well as methods for the treatment of aging, disease, or other conditions by the in vivo administration of a formulation, such as a fusogenic LPN formulation, comprising an expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, in a target cell that is associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell.

An isolated polypeptide comprising an amino acid sequence corresponding to the amino acid residues forming a full or partial -helical domain, the hinge domain, the -triple spiral domain and a full or partial globular head domain of an avian reovirus sigma C protein, and lacking the amino acid sequence that is N-terminal to said -helical domain is provided. Furthermore, a vaccine comprising, or a viral vector expressing, at least one of the isolated polypeptides of the present invention is provided.

Provided is a method for producing an artificial recombinant virus of the family Reoviridae, the method comprising the steps of: (1) introducing a FAST protein expression vector and/or a capping enzyme expression vector into host cells; (2) introducing a vector containing expression cassettes for individual RNA genome segments of a virus or introducing a set of single-stranded RNA transcripts from the expression cassettes into host cells; and (3) culturing the host cells.

The method of the present invention allows more efficient production of an artificial recombinant virus of the family Reoviridae as compared with conventional methods and allows artificial recombinant rotavirus production without using a helper virus.

The present invention relates to an attenuated reovirus-based vaccine composition and a use thereof, the attenuated reovirus, according to the present invention, having the 251st to 455th amino acids of a sigma-1 protein of a capsid truncated such that when an epitope of an antigenic protein inducing cancer or infectious disease is introduced to the truncated site of the sigma-1 protein, the epitope of the antigenic protein is stably expressed in a cell, and thus the effect is gained of exhibiting an immune response such as producing a neutralizing antibody or inducing cell-mediated immunity. As such, the present invention is expected to be usefully employable as a vaccine composition for cancer or infectious disease by introducing the epitope of the antigenic protein to the truncated site of the sigma-1 protein of the attenuated reovirus according to the present invention.

The present disclosure provides a method of producing a negative-strand RNA virus vector. The present disclosure specifically provides a method of producing a negative-strand RNA virus vector in the presence of a PKR inhibitory factor.

Disclosed are recombinant oncolytic viruses that express one or more reovirus fusion-associated small transmembrane FAST) proteins and uses thereof. The oncolytic activity of the recombinant oncolytic viruses expressing FAST proteins can be used to treat primary and metastatic cancers, especially from breast and colon cancers.