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mRNA Aerosol Delivered to Lungs to Treat Pneumonia

Inspecting lung X-rays

(National Heart, Lung, and Blood Institute, NIH)

28 Feb. 2023. Messenger RNA, inhaled from an aerosol spray, is shown in lab rats with pneumonia to reduce inflammation, improve lung functions, and protect against further infections. A team from University of Galway in Ireland and the biotechnology company Factor Bioscience Inc. in Cambridge, Massachusetts conducting the study published its findings in the 22 Feb. issue of the journal Nucleic Acid Therapeutics.

Messenger RNA or mRNA is a single strand of nucleic acid transcribed from the genetic code in DNA with instructions in cells for producing specific amino acids in proteins. Synthesized mRNA is being studied and implemented in vaccines and treatments, most notably for infectious diseases such as Covid-19, and immunotherapies for cancer and other diseases. In most cases up to now, mRNA is delivered with injections or infusions, but other delivery methods are now being investigated. As reported in Science & Enterprise in Jan. 2019, researchers at MIT and the company Translate Bio developed an inhaled nanoscale form of mRNA for treating lung diseases.

Factor Bioscience is a developer of cell and gene therapies, but also methods for delivery of nucleic acids to treat disease. The company, founded in 2011, says it’s developing a number of processes for transferring mRNA and other nucleic acids for treatments to cells in the skin, eyes, and lungs, both in vivo and ex vivo, or inside and outside the body, that overcome cell entrapment and toxicity limitations.

Express therapeutic proteins in four hours

In the new paper, researchers from Factor Bio and the CÚRAM research center at University of Galway that studies medical device technologies, tested techniques for delivering mRNA as an aerosol spray into the lungs. The team prepared a form of mRNA with instructions for proteins that protect against oxidative stress in the lungs and elsewhere in the body. In earlier preclinical studies with lab animals these same proteins coded first in mRNA and delivered as a vaccine with benign viruses reduce severity of pneumonia symptoms.

To produce the aerosol, the researchers formulated mRNA with a lipid or natural oil that neutralizes the polarity of the nucleic acids, then forced mRNA-lipid compound through a vibrating mesh atomizer to produce a fine spray with nanoscale particles. The team first tested the mRNA aerosol in lab cultures on epithelial cells that line the lungs, showing cells exposed to the spray began expressing therapeutic proteins within four hours, and reduced inflammatory biomarkers and offered more antioxidant protection within 48 hours.

In tests with lab rats, induced with acute respiratory distress syndrome or ARDS from pneumonia caused by E. coli infections, the researchers randomly assigned the animals to receive the mRNA aerosol spray coded for the therapeutic proteins or a spray with scrambled mRNA molecules for comparison. The researchers found rats receiving the therapeutic mRNA aerosol spray show better functioning lungs, with decreased bacterial load and lower levels of inflammatory cytokines than the comparison group receiving scrambled mRNA.

The authors conclude aerosol mRNA is a promising treatment for ARDS from pneumonia. “There are currently no effective specific therapies for ARDS,” says University of Galway research fellow and senior author Daniel O’Toole in a Factor Bio statement, “and the mortality rate remains high. The ability to directly express anti-inflammatory proteins in lung tissue makes aerosolized mRNA an attractive candidate therapy for pneumonia.” O’Toole adds, “In particular, the speed with which cells express proteins when treated with mRNA is particularly important in the context of a rapid-onset disease such as ARDS.”

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