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Lipid‐Modified Aminoglycosides for mRNA Delivery to the Liver by Xueliang Yu; Shuai Liu; Qiang Cheng; Tuo Wei; Sang Lee; Di Zhang; Daniel J. Siegwart is a Engineering article available to read on EtoBox.

What is Lipid‐Modified Aminoglycosides for mRNA Delivery to the Liver about?

Cationic lipid nanoparticles (LNPs) are widely used as carriers for delivery of nucleic acids. Most synthetic routes toward cationic lipids have derived from simple amine cores. Greater chemical diversity can be obtained through starting with natural products containing basic nitrogen atoms, which offers routes to more complex molecules. Natural building blocks are not extensively explored, such as aminoglycosides, which are both structurally and functionally interesting for developing new carriers for nucleic acid delivery. Herein, cationic lipid-modified aminoglycosides (CLAs) are explored as a family of vehicles for messenger RNA (mRNA) delivery. CLAs are synthesized from natural existing aminoglycosides coupling with alkyl epoxides and acrylates. The top hit (GT-EP10) is able to deliver Luc mRNA to C57BL/6 mice at a dose of 0.05 mg kg to achieve a 10 average luminescence intensity in the liver. The Lox-Stop-Lox tdTomato mouse model is used to further demonstrate that this efficient mRNA delivery system can be potentially used for gene editing. Successful delivery of human erythropoietin mRNA shows that CLA-based LNPs have promising opportunities for delivery of therapeutic nucl

Who reads Lipid‐Modified Aminoglycosides for mRNA Delivery to the Liver?

Author

Xueliang Yu; Shuai Liu; Qiang Cheng; Tuo Wei; Sang Lee; Di Zhang; Daniel J. Siegwart

Publisher

Wiley (John Wiley & Sons); John Wiley and Sons Ltd; Wiley (ISSN 2192-2640)

Published

2020

Language

EN

Field

Engineering (Physical Sciences)