Hung Trinh: In Vivo Success, Enhanced mRNA Delivery via Cyclic Disulfide-Containing LNPs
Hung Trinh, Senior VP of Operations at Seneca Therapeutics, shared a post on LinkedIn:
“In vivo demonstration of enhanced mRNA delivery by cyclic disulfide-containing lipid nanoparticles for facilitating endosomal escape
Current LNP technology faces challenges that must be addressed to enhance the functionality of mRNA therapeutics. Recent studies show disulfide-conjugated molecules improve cell membrane permeability. Here, we investigated incorporating cyclic disulfide (CDL) units into lipid components of LNPs to enhance LNP-mRNA performance.
A lipid library with branched and unbranched alkyl chains (C16–C20) and tertiary amine groups modified with CDLs was designed. While cellular uptake was unchanged, some mRNA-loaded LNPs with CDLs achieved more than 2-fold higher transfection efficiency than LNPs with MC3 or SM102 alone. Intracellular analysis revealed that the addition of CDL lipids significantly promoted endosomal escape. The CDL-incorporated LNPs administered subcutaneously in mice showed significantly higher luciferase gene expression compared to LNPs without CDL.
Additionally, LNPs encapsulating OVA antigen-encoding mRNA induced a potent antitumor response against the EG7-OVA lymphoma model. These results suggest CDL modifications enhance LNP-based mRNA delivery, offering potential for broader therapeutic applications and improved clinical outcomes.”
Title: In vivo demonstration of enhanced mRNA delivery by cyclic disulfide-containing lipid nanoparticles for facilitating endosomal escape
Authors: Seigo Kimura, Kana Okada, Noriaki Matsubara, Fangjie Lyu, Susumu Tsutsumi, Yasuaki Kimura, Fumitaka Hashiya, Masahito Inagaki, Naoko Abe, Hiroshi Abe
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