A new mRNA therapy that prompts the body to produce bacteria-killing ‘peptibodies’ has shown early success in preclinical models, offering a potential new tool in the fight against antibiotic-resistant pneumonia.
A team of researchers at the Icahn School of Medicine at Mount Sinai and collaborating institutions has reported encouraging early results for a novel mRNA-based therapy aimed at combating antibiotic-resistant bacteria – a growing and global threat that kills more than a million people annually.
The study demonstrated that the therapy slowed bacterial growth, boosted immune responses and reduced lung damage in preclinical models of multidrug-resistant pneumonia. This included mouse studies and tests using human lung tissue in the laboratory.
A growing global health crisis
Antibiotic-resistant infections continue to grow worldwide, with more than 1.2 million deaths attributed directly to resistant bacteria each year and almost 5 million deaths associated with related complications. In the United States alone, these infections cause more than 3 million illnesses and up to 48,000 deaths annually, while generating billions of dollars in healthcare costs.
Antibiotic-resistant infections continue to grow worldwide, with more than 1.2 million deaths attributed directly to resistant bacteria each year and almost 5 million deaths associated with related complications.
Experts warn that resistance is rising across nearly all major bacterial species, threatening the safety of routine surgeries, cancer treatments and neonatal care.
“Our work suggests there may be a new path to tackling antibiotic-resistant infections by supporting the immune system more directly,” says Dr Xucheng Hou, lead author of the study and Assistant Professor of Immunology and Immunotherapy at the Icahn School of Medicine 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.”
How the therapy works
The approach centres on delivering mRNA that instructs the body to produce a unique infection-fighting protein known as a ‘peptibody.’ This engineered molecule is designed to disrupt harmful bacteria directly and recruit immune cells to help clear infections.
To ensure the mRNA reaches the correct cells, researchers packaged it inside lipid nanoparticles.
To ensure the mRNA reaches the correct cells, researchers packaged it inside lipid nanoparticles – the same type of fat-based delivery vehicles used in many mRNA vaccines. These nanoparticles shield the mRNA as it travels through the body and help it enter cells.
The formulation also contains an ingredient that helps neutralise reactive oxygen species – highly reactive molecules produced during infection that can damage tissue and worsen symptoms
Promising preclinical results
In mouse models of multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa, repeated doses of the therapy were well tolerated. The treatment reduced bacterial burden in the lungs, diminished inflammation and helped maintain healthy lung structure.
Tests in human lung tissue produced similar results, showing that the peptibody-producing mRNA could function effectively alongside human immune cells.
What’s next?
Next steps include continuing preclinical evaluation and progressing towards human clinical trials to assess safety, dosing and therapeutic potential.
“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,” says 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.”
Related topics
Antibiotics, Antimicrobials, Biotherapeutics, Drug Delivery, Drug Development, Immunology, Microbiology, Molecular Biology, Nanomedicine, Nanoparticles, Nanotechnology, Therapeutics, Translational Science