Lipid nanoparticles deliver mRNA to the blood-brain barrier  

作　　者：Yanina Kuzminich Avraham Shakked Randi Calkins Sebastian Rudden Camille Jones Jessie Doan Bora Jang Elisa Schrader Echeverri Ryan Zenhausern Liming Lian David Loughrey Hannah E.Peck Rachelle Wiese Dorothy Koveal Philip J.Santangelo James E.Dahlman 

机构地区：[1]George C.Woodruff School of Mechanical Engineering,Georgia Institute of Technology,Atlanta,GA 30332,USA [2]Parker H.Petit Institute for Bioengineering and Biosciences,Georgia Institute of Technology,Atlanta,GA 30332,USA [3]Wallace H.Coulter Department of Biomedical Engineering,Emory University School of Medicine and Georgia Institute of Technology,Atlanta,GA 30332,USA

出　　处：《Nano Research》2024年第10期9126-9134,共9页纳米研究（英文版）

基　　金：funded by the CMT Research Foundation(awarded to James E.Dahlman);supported by the Emory University Robert P.Apkarian Integrated Electron Microscopy Core Facility(RRID:SCR_023537);supported by the National Science Foundation Major Research Instrumentation(No.0923395).

摘　　要：Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous administration.These clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).However,delivery to the CNS has been difficult,in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains challenging.Here we report methods to isolate different cell types from the CNS,and subsequently present mRNA delivery readouts using a liver-detargeted LNP.These data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous administration.Given the difficulty of crossing the blood-brain barrier,they also underscore the value of quantifying delivery in the CNS with cell-type resolution instead of whole-tissue resolution.

关 键 词：lipid nanoparticle MRNA NANOMEDICINE central nervous system blood-brain barrier 

分 类 号：TB383[一般工业技术—材料科学与工程]