Researchers on the Icahn Faculty of Drugs at Mount Sinai and collaborators have reported early success with a novel mRNA-based remedy designed to fight antibiotic-resistant micro organism.
The findings, revealed in Nature Biotechnology, present that in preclinical research in mice and human lung tissue within the lab, the remedy slowed bacterial progress, strengthened immune cell exercise, and diminished lung tissue injury in fashions of multidrug-resistant pneumonia.
The rising menace of resistance
Antibiotic-resistant infections are a rising international menace, killing greater than 1.2 million individuals annually and contributing to almost 5 million deaths worldwide. In america alone, greater than 3 million infections happen yearly, inflicting as much as 48,000 deaths and costing billions of {dollars} in well being care. Consultants warn that resistance is rising throughout almost all main bacterial species, placing routine surgical procedures, most cancers remedies, and new child care in danger.
“Our work suggests there could also be a brand new path to tackling antibiotic-resistant infections by supporting the immune system extra instantly,” says Xucheng Hou, Ph.D., a lead writer of the examine and Assistant Professor of Immunology and Immunotherapy within the lab of Yizhou Dong, Ph.D., on the Icahn Faculty of Drugs at Mount Sinai.
“Though we’re nonetheless within the early phases and have solely examined this strategy in preclinical fashions, the outcomes lay necessary groundwork for future therapies that would improve how conventional antibiotics carry out.”
How the experimental remedy works
The experimental remedy works by giving the affected person mRNA that instructs their physique to make a particular infection-fighting protein referred to as a “peptibody.” This peptibody is designed to do two issues on the an infection website: instantly break down dangerous micro organism and recruit immune cells to assist clear them out.
To get the mRNA safely into the affected person’s physique, the researchers packaged it inside lipid nanoparticles—tiny fat-based bubbles generally utilized in mRNA vaccines. These nanoparticles defend the mRNA because it travels via the physique and assist it enter cells.
Additionally they carry an additional ingredient that helps restrict dangerous irritation by neutralizing extra reactive oxygen species, extremely reactive molecules that the physique produces throughout an infection and that may injury tissues, usually contributing to the extreme signs of hard-to-treat infections.
Outcomes from preclinical research
In mouse fashions of multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa, repeated doses of the remedy had been nicely tolerated, diminished bacterial numbers within the lungs, decreased irritation, and preserved regular lung construction, the investigators report. As well as, the laboratory assessments with human lung tissue confirmed comparable outcomes, demonstrating that the remedy might work alongside human immune cells.
Subsequent, the researchers plan to proceed preclinical research and ultimately advance towards human medical trials to guage security, dosing, and efficacy. Whereas the remedy remains to be in early phases, it represents an encouraging path within the international struggle towards antibiotic-resistant infections.
Potential for future remedies
“That is the primary proof that an mRNA-encoded antimicrobial peptide can instantly kill micro organism whereas additionally turning on the immune system’s protecting responses,” says Dr. Dong, the senior writer and a co-corresponding writer of the examine, Mount Sinai Professor in Nanomedicine, and a member of the Icahn Genomics Institute and the Marc and Jennifer Lipzhultz Precision Immunology Institute (PrIISM) on the Icahn Faculty of Drugs at Mount Sinai.
“If future research bear this out, it might open the door to a extremely adaptable platform for growing new remedies towards infections that not reply to immediately’s antibiotics.”
The examine’s authors, as listed within the journal, are Yonger Xue, Xucheng Hou, Siyu Wang, 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.
Extra info: Antimicrobial peptide supply to lung as peptibody mRNA in anti-inflammatory lipids treats multidrug-resistant bacterial pneumonia, Nature Biotechnology (2025). DOI: 10.1038/s41587-025-02928-x.
Supplied by The Mount Sinai Hospital
