FL0445 is a biodegradable, multi-branched ionizable lipid featuring an ionizable amine-containing headgroup together with ester and carbonate linkages. When formulated with DOPE, cholesterol, and a PEG lipid, FL0445-LNP enabled efficient delivery of both linear mRNA and structurally constrained capped circular RNA (Cap-cirRNA). In the reported study, the optimized formulation produced substantially higher in vitro protein expression than benchmark LNPs based on MC3, SM-102, or ALC-0315 and demonstrated functional nucleic-acid delivery following intravenous, intramuscular, and subcutaneous administration in mice. The platform was also evaluated for mRNA vaccination, ASO-mediated gene silencing, pDNA delivery, and GLP-1-encoding Cap-cirRNA. FL0445-LNP induced comparatively low inflammatory cytokine responses and showed favorable single-dose tolerability in the tested mouse models, supporting its further evaluation as a versatile preclinical delivery lipid for mRNA, circular RNA, and other nucleic-acid modalities.
