Delivery of mRNA to platelets using lipid nanoparticles

Abstract

Platelets are natural delivery vehicles within the blood, carrying and releasing their contents at sites of vasculature damage. Investigating the biology of platelets, and modifying them for new therapeutic uses, is limited by a lack of methods for efficiently transfecting these cells. The ability of four different classes of lipid nanoparticles (LNPs) to deliver mRNA to platelets was compared using confocal microscopy, flow cytometry and quantitative PCR. The amount of mRNA delivered, mechanism of uptake, and extent of platelet activation depended on the LNP formulation and platelet storage conditions. Cationic LNPs (cLNPs) delivered mRNA to the largest percentage of platelets but induced platelet activation. Ionizable cationic LNPs (icLNPs) delivered mRNA to fewer platelets and did not induce activation. Furthermore, mRNA delivered using icLNPs and cLNPs was stable in resting platelets and was released in platelet microparticles under specific conditions. The results demonstrate that mRNA can be delivered to platelets using cLNPs and icLNPs without impairing platelet aggregation or spreading. Optimizing the LNP formulations used here may lead to a transfection agent for platelets that allows for de novo synthesis of exogenous proteins in the future.