Synthetic Biology Breakthrough: Building a Virus to Save Pigs

The global pig farming industry faces a persistent threat from the Pseudorabies virus (PRV), a pathogen responsible for severe disease in swine and significant economic losses. While genome editing is essential for creating safer vaccines, PRV has proven notoriously difficult to manipulate due to its complex, repetitive genetic sequences and extraordinarily high ‘GC-content’—a chemical feature that makes the DNA strands difficult to separate and modify.

In a recent study, scientists developed a sophisticated assembly platform to overcome these barriers using yeast-based transformation-associated recombination (TAR). Rather than tackling the massive genome all at once, the team divided the DNA of a prevalent viral strain into nine manageable fragments. These pieces were cloned into vectors and then recombined into larger sections, effectively piecing together the biological code from scratch.

To demonstrate the system’s flexibility, the researchers utilised CRISPR/Cas9—a precise gene-editing tool—to insert a specific marker gene into the viral DNA. The result was the ‘rescue’ of a functional synthetic virus, named PRV-GX-Syn1. Although this synthetic variant produced smaller plaques and lower viral levels in lab cultures compared to its natural parent, it remained structurally indistinguishable and equally lethal in mouse models, causing comparable lung pathology.

This achievement offers a vital new tool for veterinary medicine. By enabling faster and more flexible modification of the PRV genome, this TAR-based platform facilitates advanced basic research and the rapid development of attenuated vaccines to protect livestock.