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Nanoparticles Deliver mRNA Therapy to the Lungs

April 18th, 2023 Conn Hastings Genetics, Medicine, Nanomedicine, News

Researchers at MIT have developed lipid nanoparticles that are highly efficient at delivering mRNA therapies to lung cells. Getting therapeutic agents into the lungs can be challenging, but there are a variety of medical challenges that could be addressed by efficiently targeting lung cells with nanoparticle technologies. These latest particles are highly efficient at delivering mRNA which can then encode therapeutically useful proteins in the lungs. So far, the researchers have demonstrated that the particles can deliver mRNA that codes for the CRISPR/Cas gene editing system, suggesting that the new method may be useful in treating genetic diseases that affect the lungs, such as cystic fibrosis.   

Designing nanoparticles that can treat the lungs is challenging. Typically, the particles must be engineered so that they can be inhaled, and then, once they reach the target cells, they must be able to successfully deliver their cargo to the cell interior. While it can be difficult to achieve all these parameters, doing so successfully could unlock new treatments for pulmonary disease, such as cystic fibrosis.

mRNA technology has demonstrated its utility in COVID-19 vaccines, so these MIT researchers have packaged this technology into a new type of nanoparticle that can target pulmonary disease. “This is the first demonstration of highly efficient delivery of RNA to the lungs in mice,” said Daniel Anderson, a researcher involved in the study. “We are hopeful that it can be used to treat or repair a range of genetic diseases, including cystic fibrosis.”

While mRNA itself could go some way to ameliorating issues caused by malfunctioning genes by producing a protein that was otherwise missing, for example, the CRISPR/Cas gene editing system could cut faulty genes out altogether, and replace them with a functional copy of the gene. These researchers have cunningly exploited this, by including mRNA in their particles that encodes for the CRISPR/Cas proteins, allowing lung cells to create the machinery needed to edit their own genetic material.

The lipids that make up the nanoparticles contain a positive headgroup and a negative lipid tail. The positive head helps to bind the negatively charged mRNA and lets it escape the nanoparticle once it is inside the cell, while the negative tail allows the particles to pass through the cell membrane. In tests with mice, the researchers reported that approximately 40% of lung cells were successfully treated with one dose of the particles, which increased to 60% after three doses.  The researchers hope that this highly efficient delivery will make a positive difference for patients if the therapy makes it to the clinic.

Study in journal Nature Biotechnology: Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing

Via: MIT

Image: iStock, edited by MIT News

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Conn Hastings

Conn Hastings received a PhD from the Royal College of Surgeons in Ireland for his work in drug delivery, investigating the potential of injectable hydrogels to deliver cells, drugs and nanoparticles in the treatment of cancer and cardiovascular diseases. After achieving his PhD and completing a year of postdoctoral research, Conn pursued a career in academic publishing, before becoming a full-time science writer and editor, combining his experience within the biomedical sciences with his passion for written communication.

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