Pitt neurobiologist Or Shemesh has been awarded a three-year, $400,000 NIH Trailblazer Award from the National Institute of Biomedical Imaging and Bioengineering to develop a unique platform that could pave the way for healing neurodegeneration and brain-based disorders by genetically modifying different types of glia, a class of cells that supports and protects the brain’s neurons.
Scientists have made progress in using traditional vectors to deliver genes to neurons, but that viral approach hasn’t been ideal in glia, which includes astrocytes, oligodendrocytes, microglia, and other cell types, said Shemesh, assistant professor of neurobiology.
“Glia cells are pivotal to the development of brain disease, so approaches that alter their activity could lead to new treatments,” he explained. “For our project, we are going to design a novel nonviral gene delivery vector targeting microglia or astrocytes exclusively by bioengineering modified RNAs” or ModRNAs.
ModRNAs are synthetic RNAs that are directly translated into proteins by cellular machinery, circumventing the possibility of triggering an immune response when a virus is used to transport DNA into the cell.
To show the concept works, Shemesh’s team will use their Glia RNA-vector technology to increase or decrease the activity of disease-relevant genes in either astrocytes or microglia of the mouse brain.
“We are seeing more research, including from Pitt, that indicates astrocytes and other glia play an important role in the development of Alzheimer’s disease,” Shemesh said. “So our new platform could one day provide a unique strategy to treat dementia.”