A novel mRNA-based therapy could offer a new way to combat antibiotic-resistant infections

A novel mRNA-based therapy could offer a new way to combat antibiotic-resistant infections

Researchers at the Icahn School of Medicine at Mount Sinai and colleagues have reported initial success with a novel mRNA-based therapy to combat antibiotic-resistant bacteria.

The results were published in the online edition of November 26thNatural biotechnology [DOI: 10.1038/s41587-025-02928-x] show that in preclinical studies in mice and human lung tissue in the laboratory, the therapy slowed bacterial growth, boosted immune cell activity and reduced lung tissue damage in models of multidrug-resistant pneumonia.

Antibiotic-resistant infections are a growing global threat, killing more than 1.2 million people each year and leading to nearly 5 million deaths worldwide. In the United States alone, more than 3 million infections occur annually, causing up to 48,000 deaths and costing billions of healthcare dollars. Experts warn that resistance is increasing in almost all major bacterial species, threatening routine surgeries, cancer treatments and newborn care.

“Our work suggests that there may be a new way to combat antibiotic-resistant infections by supporting the immune system more directly,” says Xucheng Hou, Ph.D., lead author of the study and assistant professor of immunology and immunotherapy in the laboratory of Yizhou Dong, Ph.D., at the Icahn School of Medicine at Mount Sinai. “Although we are still in the early stages and have only tested this approach in preclinical models, the results lay important foundations for future therapies that could improve the performance of traditional antibiotics.”

The experimental therapy involves giving the patient mRNA, which instructs their body to make a special infection-fighting protein called “peptibody.” This peptide body is designed to do two things at the site of infection: break down harmful bacteria directly and recruit immune cells to eliminate them.

To deliver the mRNA safely 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 penetrate cells. They also contain an additional ingredient that helps limit harmful inflammation by neutralizing excess reactive oxygen species, highly reactive molecules that the body produces during an infection and that can damage tissues, often contributing to the severe symptoms of difficult-to-treat infections.

In mouse models of multidrug-resistantStaphylococcus aureusAndPseudomonas aeruginosaRepeated doses of therapy were well tolerated, reduced bacterial counts in the lungs, reduced inflammation, and preserved normal lung structure, the researchers report. In addition, the laboratory tests on human lung tissue showed similar results and showed that the therapy could work in conjunction with human immune cells.

Next, researchers plan to continue preclinical studies and eventually move to human clinical trials to evaluate safety, dosage and effectiveness. Although the therapy is still in its early stages, it represents an encouraging direction in the global fight against antibiotic-resistant infections.

This is the first evidence that an mRNA-encoded antimicrobial peptide can directly kill bacteria while activating the immune system's protective responses. If future studies confirm this, it could open the door to a highly adaptable platform for developing new treatments for infections that are no longer responsive to today's antibiotics.”

Dr. Yizhou Dong, PhD, senior author and study co-author, Mount Sinai Professor of Nanomedicine and member of the Icahn Genomics Institute and the Marc and Jennifer Lipzhultz Precision Immunology Institute (PrIISM) at the Icahn School of Medicine at Mount Sinai

The article is titled “Antimicrobial peptide delivery to the lung as peptibody mRNA in anti-inflammatory lipids treats multidrug-resistant bacterial pneumonia.”

The study authors listed in the journal are Yonger Xue,

This work is supported in part by the Maximizing Investigators’ Research Award (R35GM144117) from the National Institute of General Medical Sciences.

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