Lipid nanoparticles deliver mRNA to the blood-brain barrier

被引：2

作者：

Kuzminich, Yanina ^{[1
,2
]}

Shakked, Avraham ^{[3
,4
]}

Calkins, Randi ^{[3
,4
]}

Rudden, Sebastian ^{[2
,3
,4
]}

Jones, Camille ^{[3
,4
]}

Doan, Jessie ^{[3
,4
]}

Jang, Bora ^{[3
,4
]}

Echeverri, Elisa Schrader ^{[3
,4
]}

Zenhausern, Ryan ^{[3
,4
]}

Lian, Liming ^{[3
,4
]}

Loughrey, David ^{[3
,4
]}

Peck, Hannah E. ^{[3
,4
]}

Wiese, Rachelle ^{[3
,4
]}

Koveal, Dorothy ^{[3
,4
]}

Santangelo, Philip J. ^{[3
,4
]}

Dahlman, James E. ^{[3
,4
]}

机构：

[1] Georgia Inst Technol, George C Woodruff Sch Mech Engn, Atlanta, GA 30332 USA

[2] Georgia Inst Technol, Parker H Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA

[3] Emory Univ, Wallace H Coulter Dept Biomed Engn, Sch Med, Atlanta, GA 30332 USA

[4] Georgia Inst Technol, Atlanta, GA 30332 USA

来源：

NANO RESEARCH | 2024年

基金：

美国国家科学基金会;

关键词：

lipid nanoparticle; mRNA; nanomedicine; central nervous system; blood-brain barrier; IN-VIVO; DISCOVERY; POTENT; CELLS;

D O I：

10.1007/s12274-024-6827-7

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

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.

引用

页码：9126 / 9134

页数：9

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