Methods to create barcoded influenza viruses without disrupting the function of the viral proteins and the proper packaging of the viral genome segments are described. The barcoded influenza viruses can be used within deep mutational scanning libraries to map influenza resistance mutations to therapeutic treatments. The libraries can also be used to predict influenza strains that may become resistant to therapeutic treatments and/or more easily evolve to infect new species. The libraries include features that allow efficient collection and assessment of informative data, obviating bottlenecks of previous approaches.

Modified influenza virus neuraminidases are described herein that improve viral replication, thus improving the yield of vaccine viruses. Expression of such modified neuraminidases by influenza virus may also stabilize co-expressed hemagglutinins so that the hemagglutinins do not undergo mutation or decrease the need for HA binding to cells.

The present invention relates to a mutated virus. Said virus can be an influenza virus of human or other animal origin. The present invention also relates to a method for preparing the mutated virus, the method comprising introducing UAG codons into positions upstream of the stop codons per se of one or more genes of a viral genome by reverse genetic techniques. The present invention further relates to uses of the mutated virus, for example, as a live attenuated vaccine, or in replication of controllable and safe virus models, and the like.

This disclosure provides modified cytosine deaminases (CDs). The disclosure further relates to cells and vector expressing or comprising such modified CDs and methods of using such modified CDs in the treatment of disease and disorders.

A process for the purification of influenza virus or derivative thereof requires providing a source of influenza virus or derivative thereof, optionally subjecting the source to a pre-purification step, followed by subjecting the source to at least one chromatographic step on chromatographic material selected from the group consisting of porous particles having mean pore sizes of at least 20 nm, perfusion particles, gel-in-a-shell particles, tentacle like particles, membrane adsorbers, and monoliths, and collecting fractions eluted from the chromatographic material that contain the influenza virus or derivative thereof, excluding sulfuric ester of cellulose or cross-linked polysaccharides.

The present invention describes a viral RNA expression plasmid and a method for obtaining viral particles based on the plasmids comprising transfecting animal cells with an expression vector or a set of expression vectors capable of expressing a nucleoprotein and RNA-dependent polymerase RNA; and transfecting the animal cell with an expression vector or a set of expression vectors with nucleotide sequences encoding recombinant RNA molecules.

Modified influenza virus neuraminidases are described herein that improve viral replication, thus improving the yield of vaccine viruses. Expression of such modified neuraminidases by influenza virus may also stabilize co-expressed hemagglutinins so that the hemagglutinins do not undergo mutation or decrease the need for HA binding to cells.

Methods to create barcoded influenza viruses without disrupting the function of the viral proteins and the proper packaging of the viral genome segments are described. The barcoded influenza viruses can be used within deep mutational scanning libraries to map influenza resistance mutations to therapeutic treatments. The libraries can also be used to predict influenza strains that may become resistant to therapeutic treatments and/or more easily evolve to infect new species. The libraries include features that allow efficient collection and assessment of informative data, obviating bottlenecks of previous approaches.

Expression of a transgene is driven in a host cell using a pol I promoter which is not endogenous to an organism from the same taxonomic order from which the host cell is derived.

This disclosure provides modified cytosine deaminases (CDs). The disclosure further relates to cells and vector expressing or comprising such modified CDs and methods of using such modified CDs in the treatment of disease and disorders.