Nanoparticle-delivered RNA reduces neuroinflammation in lab tests

Some COVID-19 vaccines safely and effectively used lipid nanoparticles (LNPs) to deliver messenger RNA to cells. A new MIT study shows that different nanoparticles could be used for a potential Alzheimer's disease (AD) therapy.

In tests in multiple mouse models and with cultured human cells, a newly tailored LNP formulation effectively delivered small interfering RNA (siRNA) to the brain's microglia immune cells to suppress the expression of a protein linked to excessive inflammation in Alzheimer's disease.

In a prior study, the researchers showed that blocking the consequences of PU.1 protein activity helps to reduce Alzheimer's disease-related neuroinflammation and pathology. The new results, reported in the journal Advanced Materials, achieve a reduction in inflammation by directly tamping down expression of the Spi1 gene that encodes PU.1.

More generally, the new study also demonstrates a new way to deliver RNA to microglia, which have been difficult to target so far.

"MG-LNP delivery of anti-PU.1 siRNA can potentially be used as an anti-inflammatory therapeutic in mice with systemic inflammation and in the CK-p25 mouse model of AD-like neuroinflammation," the scientists concluded, calling the results a "proof-of-principle." More testing will be required before the idea can be tried in human patients.

Image source: GerryShaw, Wikimedia Commons, CC BY-SA 4.0.