Designer mRNAs to Fight Pathogens in the Lung
Combining their expertise, Xiling Shen, Electrical and Computer Engineering, and David G. Russell, Microbiology and Immunology, have hypothesized a new therapeutic treatment for a very old disease: tuberculosis (TB), which still takes over one million lives each year in mostly undeveloped countries. Shen and Russell, along with researchers at the Georgia Institute of Technology, plan to develop synthetic mRNA that, once delivered to the lung, will express multiple therapeutic proteins and antibodies to attack the bacterium that causes TB. The method could also be used to treat other bacterial and viral infections in the lung and increase immunity. In short, the project will open the door to a suite of genetic methods for combating both viral and bacterial pathogens.
The properties and dynamics of mRNA, Shen and Russell argue, make it particularly well-suited for the job. One of the aims of the study will be to demonstrate the safety of mRNA-based expression of antibodies in the lung and to provide optimized mRNA designs, formulations, and delivery strategies that avoid and prevent inflammation. Finding the right mRNA sequences for protein production and kinetics within the lung in vivo—within epithelial cells, macrophages, and plasma—will be a particular focus.
Shen and Russell will also introduce into the lung and observe the effect of specific proteins and antibodies on tuberculosis pathogenesis and will evaluate host protein and peptide expression and its interaction with TB. In addition, the impact of other common antibodies—that combat influenza, respiratory syncytial virus, and Ebola—will be expressed and measured in the lung and plasma, providing valuable data for future anti-viral applications.