The invention provides a recombinant RNA molecule comprising (i) a sequence of a gene-editing molecule mRNA, or a sequence of a functional fragment or derivative thereof, and (ii) at least one sequence of a coding or non-coding enrichment RNA, or a sequence of a functional fragment or derivative thereof, wherein the enrichment RNA, or functional fragment or derivative thereof, is capable of enhancing inclusion of the gene-editing molecule mRNA, or functional fragment or derivative thereof, into a retroviral particle. The invention provides a method of producing the retroviral particles of the invention, the method comprising culturing a packaging cell in conditions sufficient for the production of a plurality of retroviral particles.

Described herein are uses of fluorescent enveloped virus particles as standards in nanoscale flow cytometry applications. The virus particles comprise a fluorescent dye or a fluorescent protein. A standard ladder comprising a plurality of fluorescent enveloped virus particles of different sizes is also provided. The standards may also comprise marker(s) of interest, and may be used as controls for detection of other viruses or extracellular vesicle, e.g. in diagnostic applications. Methods of producing controls for such applications are provided, including those having desired profiles. The controls may be used for enumeration of markers on microparticles (e.g. extracellular vesicles or viruses). Also described is a modified gammaretrovirus comprising a mutation that abolishes expression of the viral glyco-Gag protein, and having a fluorescent protein inserted in-frame into the proline-rich region (PRR) of the viral env protein. The gammaretrovirus may be M-MLV bearing a mutation that abolishes expression of the glyco-Gal protein, gPr80.

The present invention relates to an oncolytic virus which is, or is derived from, a clinical isolate which has been selected by comparing the abilities of a panel of three or more clinical isolates of the same viral species to kill tumor cells of two or more tumor cell lines in vitro and selecting a clinical isolate which is capable of killing cells of two or more tumor cell lines more rapidly and/or at a lower dose in vitro than one or more of the other clinical isolates in the panel.

The present invention relates to an oncolytic virus comprising: (i) a fusogenic protein-encoding gene; and (ii) an immune stimulatory molecule-encoding gene.

The present invention relates to an oncolytic virus comprising: (i) a fusogenic protein-encoding gene and (ii) an immune stimulatory molecule-encoding gene.

The present invention provides a method of treating cancer, which comprises administering a therapeutically effective amount of an oncolytic virus, an inhibitor of the indoleamine 2,3-dioxygenase (IDO) pathway and a further antagonist of an immune co-inhibitory pathway or an agonist of an immune co-stimulatory pathway to a patient in need thereof.

The present invention relates to an oncolytic virus comprising: (i) a fusogenic protein-encoding gene; and (ii) an immune stimulatory molecule-encoding gene.

Described herein are compositions relating to alphavirus-based virus-like particles (VLPs) and methods for making and using the described VLPs. The described compositions include VLPs and vectors and cells used to produce the VLPs. Also included are related methods to produce the VLPs, to transduce cells using the VLPs, and to produce a protein or polynucleotide of interest in a target cell using the VLPs. Also described are alphavirus-based replicons that allow for expression of proteins or polynucleotides of interest in a target cell without a cytopathic effect.

Described herein are compositions relating to alphavirus-based virus-like particles (VLPs) and methods for making and using the described VLPs. The described compositions include VLPs and vectors and cells used to produce the VLPs. Also included are related methods to produce the VLPs, to transduce cells using the VLPs, and to produce a protein or polynucleotide of interest in a target cell using the VLPs. Also described are alphavirus-based replicons that allow for expression of proteins or polynucleotides of interest in a target cell without a cytopathic effect.

Covalently-linked DNA polymerases are provided.