mRNA delivery to Neutrophils by Targeted Lipid Nanoparticles (LNPs)

As a critical part of the innate immune system, neutrophils are involved in a myriad of diseases. While neutrophils play a key role in resolving inflammation and killing invading pathogens, there are many diseases where excessive neutrophil activation can lead to damage and worsening of symptoms. Our lab has developed a neutrophil-targeting platform to deliver payloads (chemical compounds or mRNA) to neutrophils in order to modify their functions. While neutrophils are terminally differentiated cells, we show that they are translationally active, albeit less so than replicating cells. We fabricated lipid nanoparticles (LNPs) carrying GFP and luciferase mRNA and conjugated them to a peptide that is specifically recognized by neutrophils. We show that these LNPs are efficiently targeted to blood neutrophils as well as immature bone marrow neutrophils and that these cells are capable of translating the mRNA encapsulated within LNPs. This platform has the ability to modify neutrophil behavior while not affecting other cell types and potentially can change the progression of numerous diseases where neutrophil behavior is dysfunctional.