New research from the Perelman School of Medicine at the University of Pennsylvania suggests that a combination of messenger RNA (mRNA) and a novel lipid nanoparticle (LNP) could potentially be used to repair lung damage.
Lung damage can result from viruses, physical trauma, or other conditions. When this damage occurs in the lower regions of the lungs, it can be difficult to treat with conventional methods, such as inhaled medications. The study, published in Nature Communications, demonstrates the feasibility of an injectable therapeutic approach.
The lungs are hard-to-treat organs because both permanent and temporary damage often happens in the deeper regions where medication does not easily reach. Even drugs delivered intravenously are spread without specificity. That makes a targeted approach like ours especially valuable.”
Elena Atochina-Vasserman, MD, PhD, Study Author and Research Assistant Professor, Infectious Diseases, University of Pennsylvania
Elena Atochina-Vasserman is also a scientist at the Penn Institute for RNA Innovation.
Lung injuries can arise from various sources, including physical trauma that leads to lung inflammation and respiratory viruses such as COVID-19, influenza, and RSV.
Viral infections, in particular, can trigger an inflammatory response, resulting in fluid accumulation in the airways, excessive mucus production, cell death, and damage to the lung lining.
Both acute and chronic lung damage can be life-threatening. According to research published in The Lancet, respiratory diseases were the third leading cause of death globally even before the COVID-19 pandemic.
A New Lipid Nanoparticle
The mRNA COVID-19 vaccines, which have been crucial in saving lives, utilized specific lipid nanoparticles to deliver the mRNA. This new study paired mRNA with a single, distinct LNP ionizable amphiphilic Janus dendrimers (IAJDs) which are derived from natural materials and were discovered by Virgil Percec, PhD, the P. Roy Vagelos Professor in Chemistry at the University of Pennsylvania.
Prior research by Percec, Atochina-Vasserman, and their colleagues at Penn demonstrated that these IAJDs exhibit organ specificity, making them suitable for delivering mRNA directly to the lungs. Once in the lungs, the mRNA directs the immune system to produce transforming growth factor beta (TGF-β), a signaling molecule crucial for tissue repair.
This research marks the birth of a new mRNA delivery platform with its own strengths and potential beyond the original mRNA LNPs. 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.”
Drew Weissman, MD, PhD, Study Co-Author, Roberts Family Professor, Vaccine Research, University of Pennsylvania
Drew Weissman is also a 2023 Nobel laureate and Director of the Penn Institute for RNA Innovation.
“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 investigating a similar strategy to combat infections in the spleen.
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