Researchers at the French biotech company Transgene have developed a method for creating chimeric viruses with potentially oncolytic properties from several poxviruses. As the team reports in "Frontiers in Bioengineering and Biotechnology" (DOI: 10.3389/fbioe.2026.1943548), it uses homologous recombination in the yeast Saccharomyces cerevisiae to recombine genome segments of various poxviruses that are not pathogenic to humans.
First, the researchers assembled a nearly complete vaccinia virus genome in yeast and showed that functional viruses could be produced from it in human cancer cells. Missing terminal sequences were supplemented with the Modified Vaccinia Virus Ankara (MVA) as a helper virus. They then combined genome material from vaccinia, cowpox, and rabbitpox viruses. Of ten yeast clones tested, five yielded infectious viruses.
The chimeric viruses differed significantly in plaque morphology, spread, and activity against human cancer cell lines. Whole-genome sequencing confirmed that individual clones contained segments from multiple parent viruses. cPOX04-12 in particular showed strong replication and pronounced formation of comet plaques, indicating increased release of extracellular viruses. The authors emphasize that the viruses do not yet contain the attenuations necessary for tumor-specific replication. However, the method provides a scalable platform for finding candidates for future oncolytic therapies.
