Cryo-EM Study Reveals Structural Advantage for Use of C-Type Adenovirus in Gene Therapy

In their quest to replicate themselves, viruses have become awfully good at tricking human cells into pumping out viral proteins. That's why scientists have been working to use viruses as forces for good: to deliver useful genes to human cells and help patients who lack important proteins or enzymes. A team of researchers led by Associate Professor Vijay Reddy at The Scripps Research Institute (TSRI) has now uncovered the structural details that make one virus a better tool for future therapies than its closely related "cousin." As Dr. Reddy and his colleagues reported in the May 10, 2017 issue of Science Advances, the structure of a less prevalent species D adenovirus may work well as a gene-delivery vector because its structure doesn't let it get spirited away to the liver, minimizing liver toxicity. The Reddy lab's study is the first to show the structural details on species D's surface that set it apart from another common subtype of adenovirus, called species C, which does travel to the liver. "Greater understanding of the structures of adenoviruses from different species will help generate better gene therapies and/or vaccine vectors," said Reddy. The Science article is titled “Cryo-EM Structure of Human Adenovirus D26 Reveals the Conservation of Structural Organization Among Human Adenoviruses.” Using an imaging technique called cryo-electron microscopy, the researchers discovered that while these two species of adenoviruses share the same shell-like core, they have different surface structures, which Dr. Reddy called "decorations" or "loops."
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