PHILADELPHIA – A combination of mRNA and a new lipid nanoparticle could help heal damaged lungs, according to new research from the at the . Viruses, physical trauma, or other problems can have serious impact on lungs, and when the damage is in the lower regions, traditional treatments, like inhaled medication, might not work. The study, published in , provides a proof of concept for an injectable therapy.
“The lungs are hard-to-treat organs because both permanent and temporary damage often happen in the deeper regions where medication does not easily reach,” said study author , research assistant professor of Infectious Diseases at Penn and scientist at the . “Even drugs delivered intravenously are spread without specificity. That makes a targeted approach like ours especially valuable.”
Lung damage can result from a variety of causes ranging from physical accidents that cause inflammation of the lungs to respiratory viruses like COVID, flu, and RSV. Viruses alone can usher in an inflammatory response setting off a buildup of fluid in the airways, excess mucus, cell death, and damage to the lining of the lungs. Whether acute or chronic, weakened lungs can be life threatening. Respiratory diseases were the third leading cause of death worldwide even before the pandemic according to research .
A new lipid nanoparticle
The life-saving mRNA COVID vaccines used unique lipid nanoparticles as the mRNA delivery system. The method in this study matched up mRNA with just one unique lipid nanoparticle—ionizable amphiphilic Janus dendrimers (IAJDs) which were derived from natural materials and discovered by , the P. Roy Vagelos Professor in Chemistry at the University of Pennsylvania. from Percec, Atochina-Vasserman, and others at Penn found that these IAJDs are organ specific which made them a good candidate to send mRNA explicitly to the lungs. When it reaches the lung, the mRNA then instructs the immune system to create transforming growth factor beta (TGF-b), a signaling molecule vital for the body to repair tissue.
“This research marks the birth of a new mRNA delivery platform with its own strengths and potential beyond the original mRNA LNPs,” said 2023 Nobel laureate , a co-author of the study, the Roberts Family Professor in Vaccine Research, and director of the Penn Institute for RNA Innovation. “While using other lipid nanoparticles works great to prevent infectious diseases, in addition to being specific to the lung, this new platform does not have to be stored at such extremely cold temperatures and is even easier to produce.”
“While this research focused on the lungs, this method is also being explored for therapies for other organs,” said Percec. Atochina-Vasserman, Weissman, and colleagues are trying a similar approach against infections that occur in the spleen.
This study was supported by the National Institutes of Health Institute of Environmental Health Sciences (T32-ES01984, P30-ES005022), the National Science Foundation (DMR-1807127, DMR-1720530, DMR-2104554), and the Wellcome Leap R3 program.
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