Schematic diagram of a 4-plasmid-based reverse genetic approach to generate vaccine seed viruses. A Pol I plasmid that synthesizes modified HA and NA gene segments is prepared from the circulating wild-type strains. Another Pol I plasmid that synthesizes the other six gene segments is prepared from a backbone virus that grows well in eggs or in cell culture. Two plasmids, expressing polymerase proteins or NP, respectively, are also prepared. Thus, a total of 4 plasmids are used to generate the vaccine seed viruses, with higher efficiency than other current systems, which can contain more than 8 plasmids.