Researchers resurrect ancient viruses in hopes of improving gene therapy

Researchers have recreated the evolutionary lineage of adeno-associated viruses (AAVs) to reconstruct an ancient viral particle that is highly effective at delivering gene therapies targeting the liver, muscle, and retina. This approach could be used to design a new class of genetic drugs that are safer and more potent than those currently available.

"Our novel methodology allows us to understand better the intricate structure of viruses and how different properties arose throughout evolution," says senior study author Luk H. Vandenberghe of Harvard Medical School. "We believe our findings will teach us how complex biological structures, such as AAVs, are built. From this knowledge, we hope to design next-generation viruses for use as vectors in gene therapy."

Viruses need to efficiently transfer their genetic material into host cells in order to replicate and survive. Researchers have taken advantage of this natural property to develop viral vectors, or carriers, capable of shuttling therapeutic genes to the appropriate cells or tissues.

Early-stage clinical trials have demonstrated the safety and effectiveness of this approach for treating inherited blindness and hemophilia. But so far, AAVs used for gene therapy have been chosen from naturally circulating viral strains, which patients may already have been exposed to, which means they would have natural immunity. Because natural immunization blocks the transfer of the therapeutic gene, these individuals are often ineligible for gene therapy.