Biodistribution of lipid nanoparticle, eGFP mRNA and translated protein following subcutaneous administration in mouse.

Increased knowledge of biodistribution and pharmacokinetics of lipid nanoparticle (LNP)-encapsulated mRNA drug components may aid efficacy and safety evaluation. Mice were subcutaneously administrated LNP encapsulated enhanced green fluorescent protein mRNA and sampled up to 72 h after dosing. LNP, mRNA and translated protein were quantified by LC-MS, branched DNA and ELISA.

Spray dried lipid nanoparticle formulations enable intratracheal delivery of mRNA.

RNA therapies have recently taken a giant leap forward with the approval of Onpattro™, a siRNA therapy delivered using a lipid nanoparticle (LNP), and the LNP-enabled mRNA vaccines against COVID-19, which are the first mRNA drugs to reach the marketplace. The latter medicines have illustrated that stability is a significant challenge in the distribution of RNA drugs using non-viral delivery systems, particularly in areas without cold chain storage. Here, we describe a proof-of-concept study on the engineering of an LNP mRNA formulation suitable for spray drying.

Functionalized lipid nanoparticles for subcutaneous administration of mRNA to achieve systemic exposures of a therapeutic protein.

Lipid nanoparticles (LNPs) are the most clinically advanced delivery system for RNA-based drugs but have predominantly been investigated for intravenous and intramuscular administration. Subcutaneous administration opens the possibility of patient self-administration and hence long-term chronic treatment that could enable messenger RNA (mRNA) to be used as a novel modality for protein replacement or regenerative therapies. In this study, we show that subcutaneous administration of mRNA formulated within LNPs can result in measurable plasma exposure of a secreted protein.

Overcoming analytical challenges to generate data critical to understanding lipid nanoparticle-delivered modified mRNA biodistribution.

Chemically modified mRNA offers a novel approach to treat disease. Due to susceptibility to extracellular nucleases , dosed modified mRNA therapeutics can benefit from encapsulation within novel delivery systems, such as lipid nanoparticles (LNPs). To understand the holistic effect of dosing LNP-encapsulated modified mRNA therapeutics can require bioanalysis of several components including the mRNA, protein and LNP.

Synthesis of di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate in unlabelled and C-13 labelled forms for use as a biomarker of drug induced phospholipidosis.

Di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) has been identified as a promising biomarker for drug-induced phospholipidosis (DIPL). Both unlabelled and stable isotope labelled versions of BMP were desired for use as internal standards. Isopropylideneglycerol was converted to 4-methoxyphenyldiphenylmethyl-3-PMB-glycerol in three steps.