Mount Sinai Researchers Develop Novel mRNA Therapy to Combat Antibiotic-Resistant Bacterial Infections
Key Insights
Researchers at Mount Sinai have developed an experimental mRNA-based therapy that successfully reduced bacterial growth and lung tissue damage in preclinical models of multidrug-resistant pneumonia (search).
The therapy delivers mRNA instructions to produce infection-fighting "peptibodies (search)" that both directly kill bacteria and recruit immune cells (search) to clear infections.
In mouse models of resistant Staphylococcus aureus (search) and Pseudomonas aeruginosa (search), the treatment was well-tolerated and preserved normal lung structure while reducing bacterial numbers.
Researchers at the Icahn School of Medicine at Mount Sinai have achieved promising preclinical results with a novel mRNA-based therapy designed to combat the growing threat of antibiotic-resistant bacterial infections. The findings, published in Nature Biotechnology on November 26, demonstrate that the experimental treatment successfully reduced bacterial growth, enhanced immune cell activity, and minimized lung tissue damage in models of multidrug-resistant pneumonia (search).
The breakthrough comes at a critical time when antibiotic-resistant infections (search) kill more than 1.2 million people annually and contribute to nearly 5 million deaths worldwide. In the United States alone, these infections cause more than 3 million cases per year, resulting in up to 48,000 deaths and billions of dollars in healthcare costs.
Dual-Action Mechanism Targets Bacteria and Immune Response
The experimental therapy works by delivering mRNA that instructs patients' cells to produce specialized infection-fighting proteins called "peptibodies (search)." These engineered proteins perform two critical functions at infection sites: directly breaking down harmful bacteria and recruiting immune cells (search) to help eliminate the pathogens.
"Our work suggests there may be a new path to tackling antibiotic-resistant infections (search) by supporting the immune system more directly," said Xucheng Hou, PhD, lead author and Assistant Professor of Immunology and Immunotherapy at Mount Sinai. "Although we're still in the early stages and have only tested this approach in preclinical models, the results lay important groundwork for future therapies that could enhance how traditional antibiotics perform."
The researchers packaged the therapeutic mRNA inside lipid nanoparticles (search)—the same type of fat-based delivery vehicles used in mRNA vaccines. These nanoparticles protect the mRNA during transport through the body and facilitate cellular uptake. Additionally, they contain components that help limit harmful inflammation by neutralizing excess reactive oxygen species (search), highly reactive molecules that can damage tissues during severe infections.
Promising Results Against Resistant Pathogens
In preclinical studies using mouse models of multidrug-resistant Staphylococcus aureus (search) and Pseudomonas aeruginosa (search), repeated doses of the therapy demonstrated encouraging safety and efficacy profiles. The treatment reduced bacterial numbers in the lungs, decreased inflammation, and preserved normal lung structure. Laboratory tests with human lung tissue yielded similar results, showing the therapy's compatibility with human immune cells (search).
"This is the first evidence that an mRNA-encoded antimicrobial peptide can directly kill bacteria while also turning on the immune system's protective responses," said Dr. Yizhou Dong, senior author and Mount Sinai Professor in Nanomedicine. "If future studies bear this out, it could open the door to a highly adaptable platform for developing new treatments against infections that no longer respond to today's antibiotics."
Path to Clinical Development
The research team plans to continue preclinical studies before advancing toward human clinical trials to evaluate safety, dosing, and efficacy. While still in early development stages, the therapy represents a potentially transformative approach in addressing the global crisis of antibiotic resistance.
The growing threat of resistant bacteria has put routine medical procedures at risk, including surgeries, cancer treatments, and newborn care. Experts warn that resistance is increasing across nearly all major bacterial species, creating an urgent need for innovative therapeutic approaches.
The study, titled "Antimicrobial peptide delivery to lung as peptibody mRNA in anti-inflammatory lipids treats multidrug-resistant bacterial pneumonia," was supported in part by the Maximizing Investigators' Research Award from the National Institute of General Medical Sciences. The research involved collaboration between multiple investigators at Mount Sinai's Icahn Genomics Institute and the Marc and Jennifer Lipzhultz Precision Immunology Institute.