Breakthrough mRNA Therapy Shows Early Success Against Antibiotic-Resistant Bacteria
Researchers from the Icahn School of Medicine at Mount Sinai and their collaborators have announced early success with a new mRNA-based treatment developed to tackle antibiotic-resistant bacteria.
Published in Nature Biotechnology, the findings reveal that in tests using mice and human lung tissue, the therapy curtailed bacterial growth, boosted immune cell response and lessened lung damage in models of multidrug-resistant pneumonia.
Growing Threat of Antibiotic Resistance
Drug-resistant infections are now a pressing global danger, claiming more than 1.2 million lives annually and contributing to almost 5 million deaths around the world. In the United States alone, these infections exceed 3 million cases each year, resulting in up to 48,000 fatalities and costing the healthcare system billions. Scientists warn that resistance continues to rise across most major bacterial strains, posing serious risks to routine medical procedures, cancer treatments and neonatal care.
Rising Global Mortality from Drug-Resistant Infections
"Our findings indicate a promising route to tackling antimicrobial resistance by boosting the body's immune defense directly," explains Xucheng Hou, Ph.D., lead author 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 this work is still in its early phase and has so far only been tested in preclinical models, it lays an essential foundation for future therapies that may improve the effectiveness of conventional antibiotics."
How the Experimental Therapy Works
The experimental treatment delivers mRNA into the body, prompting it to produce a unique infection-fighting protein known as a "peptibody." This peptibody serves a dual role at the site of infection: dismantling harmful bacteria and directing immune cells to eliminate them.
Role of Lipid Nanoparticles in Delivery
To ensure the mRNA reaches cells safely, scientists enclosed it in lipid nanoparticles—tiny, fat-based spheres frequently used in mRNA vaccines. These nanoparticles shield the mRNA as it travels through the body and assist its entry into cells.
They also contain an added component that limits damaging inflammation by neutralizing reactive oxygen species—highly reactive molecules produced during infection that can injure surrounding tissues and worsen symptoms.
Results from Preclinical Studies
In mouse models of multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa, multiple doses of the treatment were well tolerated and led to a marked reduction in bacterial levels in the lungs. The therapy also eased inflammation and helped maintain normal lung architecture.
Human Lung Tissue Findings
Similar results were seen in laboratory experiments using human lung tissue, indicating that it can operate effectively alongside human immune cells. The team will now continue preclinical work before moving towards human trials to assess safety, dosage and effectiveness. Although the technology remains in its early stages, it offers a promising new path in the global battle against antibiotic resistance.
Potential for Future Treatments
"This is the first evidence that an mRNA-encoded antimicrobial peptide can both destroy bacteria directly and activate the immune system's defensive mechanisms," says Dr Dong, senior author of the study, Professor of Nanomedicine at Mount Sinai, and a member of the Icahn Genomics Institute and the Marc and Jennifer Lipzhultz Precision Immunology Institute (PrIISM).
"If the findings are supported by further studies, this could lead to a flexible new platform for designing treatments against infections that no longer respond to standard antibiotics."
Path Toward Human Trials
The team will now continue preclinical work before moving towards human trials to assess safety, dosage and effectiveness. Although the technology remains in its early stages, it offers a promising new path in the global battle against antibiotic resistance.
Study Contributors
The study lists the authors as: Yonger Xue, Xucheng Hou, Yuebao Zhang, Yichen Zhong, Diana D. Kang, Chang Wang, Haoyuan Li, Changyue Yu, Zhengwei Liu, Meng Tian, Dinglingge Cao, Ya Ying Zheng, Binbin Deng, Pauline Hamon, Miriam Merad and Yizhou Dong.
