A naturally derived lipopeptide lipid nanoparticle platform enabling multiple nucleic acids delivery.

ABSTRACT: Lipid nanoparticles (LNPs) have emerged as versatile platforms for nucleic acid-based therapies. Despite advancements, key challenges remain in achieving tissue-specific delivery while maintaining low toxicity and tunable properties essential for therapeutic applications. Here, we report a novel high-performance LNP platform employing arginine-histidine peptide-dioleoylphosphatidylethanolamine (RmHnC-DOPE) lipopeptides as core components. Through systematic optimization of arginine-to-histidine ratios, we engineered three variants, R3H7C-DOPE, R4H6C-DOPE, and R5H5C-DOPE, enabling payload-specific and tissue-selective delivery of siRNA, mRNA, and plasmid DNA. In vitro evaluation demonstrated superior gene silencing efficiency for R4H6C-DOPE (85.1%) and R5H5C-DOPE (89.5%) compared to

SUBMITTER: Xiao H 

PROVIDER: S-EPMC12628137 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature