Rapidly Excretable Antioxidant Ionizable Lipids for Safe and Efficient mRNA Delivery
발표자
이예지 (서울대학교)
연구책임자
이혁진 (서울대학교)
공동저자
이예지 (서울대학교), 이혁진 (서울대학교)
초록
내용
Messenger RNA (mRNA) delivery is limited by the accumulation, oxidative stress, and immunogenicity of conventional lipid nanoparticles (LNPs). Here, we report rapidly excretable antioxidant ionizable lipids based on a sulfur-containing hexyl 2-hydroxyethyl sulfide (HHES) motif. HHES lipids efficiently scavenge reactive oxygen species while degrading into hydrophilic, excretable metabolites, enabling rapid systemic clearance and minimal tissue accumulation. HHES LNPs maintain robust protein expression with reduced inflammatory signaling and toxicity, and show favorable pharmacokinetics and tolerability in both systemic and subretinal delivery. They further enable efficient in vivo antibody expression and genome editing, providing a safer and broadly applicable platform for mRNA therapeutics.