Improved localized mRNA delivery using lipid nanoparticles with a novel synthetic cholesterol derivative
Year: 2025
Type: article
Abstract: transfection efficiency by approximately 10-fold and 20-fold in HEK293T and HeLa cells, respectively. Furthermore, when GA-Chol LNPs were injected intramuscularly or intratumorally, robust localized transfection was observed in either the injected muscle or the flank tumors, without significant transfection in the liver. This observation was consistent across multiple cell lines, representing various types of cancer. Leverage local delivery strategy, mRNA encoding for constitutively active caspase-3 was encapsulated with GA-Chol LNPs and delivered intratumorally in 4T1 tumor-bearing BALB/c mice, resulting in a significantly reduced and sustained tumor burden. Overall, these findings describe the potential application of a synthetic cholesterol derivative for the localized transfection of LNPs.
Source: RSC Pharmaceutics
DOI: 10.1039/d5pm00166h
Authors: Deepak K. Sahel, Jonas Renner, Kseniia Yu. Vlasova, Nathan D. Pennock, Sakib T. Haque, Antony Jozic, Joshua M. Walker, Conroy Sun, Gaurav Sahay
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4416299305