Matthew D. Weitzman, PhD, and Matthew Charman, PhD, on Studying the DNA Virus Replication Process

The investigators from Children’s Hospital of Philadelphia discussed the potential implications of their research into human adenoviruses for the development of new gene delivery tools.

“I think that the field has made such amazing progress in terms of what we do with our gene delivery tools—how we can tweak them and modify them for particular applications [or] particular treatments. But so often, we are inherently limited in what we can do with those tools because of the inherent biology of the virus. One of our overarching research missions is: If we can truly understand how viruses come together and make new viruses, if we can begin to master this process—can we actually use that information to think about designing a next generation of gene delivery tools that wouldn't suffer from the inherent limitations of the current tools?”

Although modified DNA viruses are already being utilized in investigational and approved gene therapy products for the treatment of various diseases, the fine details of the process of DNA virus replication have remained elusive to researchers. Ongoing attempts to learn these minutiae, though, are unveiling the medical field’s picture of genetics.

Matthew D. Weitzman, PhD, a professor in the Department of Pathology and Laboratory Medicine at Children's Hospital of Philadelphia (CHOP), and Matthew Charman, PhD, a research associate in the Weitzman Lab at CHOP, are among those conducting this research. Recently, they published a paper in Nature detailing the findings of their research into the DNA virus replication process. Of note, they identified the adenovirus 52 kDa protein (52K) as essential in the formation of biomolecular condensates from viral structural proteins in the human adenovirus replication process.1,2

In an interview with CGTLive™, Weitzman and Charman summarized the key findings of their research. Weitzman noted that prior to their study, it was not known whether the viral genome is replicated and then inserted into a virus particle or whether the virus particle forms around the replicated viral genome; their research revealed that the latter model is the case in human adenovirus replication. Charman added that a better understanding of how this process is initiated remains an important avenue for further study. Weitzman and Charman also discussed the potential implications of their findings for the development of new gene delivery tools that could one day be utilized in future gene therapies.

1. Charman M, Grams N, Kumar N, et al. A viral biomolecular condensate coordinates assembly of progeny particles. Nat Med. Published online April 5, 2023. doi:10.1038/s41586-023-05887-y
2. CHOP researchers reveal complex assembly process involved in DNA virus replication. News release. Children’s Hospital of Philadelphia. April 5, 2023. Accessed April 5, 2023.
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