Researchers at the Icahn School of Medicine at Mount Sinai have reported early success with a novel mRNA-based therapy designed to combat antibiotic-resistant infections.
The findings show that in preclinical studies in mice and human lung tissue in the lab, the therapy slowed the growth of antibiotic-resistant bacteria, strengthened immune cell activity, and reduced lung tissue damage in models of multidrug-resistant pneumonia.
“Our work suggests there may be a new path to tackling antibiotic-resistant infections by supporting the immune system more directly,” stated Xucheng Hou, PhD, a lead author of the study 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 growing threat of antibiotic-resistant infections
Antibiotic-resistant infections are a growing global threat, killing more than 1.2 million people each year and contributing to nearly five million deaths worldwide.
In the US alone, more than three million infections occur annually, causing up to 48,000 deaths and costing billions of dollars in health care.
Experts warn that resistance is increasing across nearly all major bacterial species, putting routine surgeries, cancer treatments, and newborn care at risk.
How a peptibody works to combat infection
The experimental therapy works by giving the patient mRNA that instructs their body to make a special infection-fighting protein called a “peptibody.” This peptibody is designed to do two things at the infection site: directly degrade harmful bacteria and recruit immune cells to help clear them.
To safely deliver the mRNA into the patient’s body, the researchers packaged it into lipid nanoparticles – tiny fat-based bubbles commonly used in mRNA vaccines. These nanoparticles protect the mRNA as it travels through the body and help it enter cells.
They also contain an extra ingredient that helps limit harmful inflammation by neutralising excess reactive oxygen species, highly reactive molecules the body produces during infection that can damage tissues and often contribute to the severe symptoms of antibiotic-resistant infections.
Lab tests revealed promising results
In mouse models of multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa, repeated doses of the therapy were well tolerated, reduced bacterial numbers in the lungs, decreased inflammation, and preserved normal lung structure.
In addition, the laboratory tests with human lung tissue showed similar results, demonstrating that the therapy could work alongside human immune cells.
“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 Dong, the senior author and a co-corresponding author of the study 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.”
Next steps: Towards human clinical trials
Next, the researchers plan to continue preclinical studies and eventually advance toward human clinical trials to evaluate safety, dosing, and efficacy.
While the therapy is still in early stages, it represents an encouraging direction in the global fight against antibiotic-resistant infections.