Quantitating Endosomal Escape of a Library of Polymers for MRNA Delivery

Overview

Journal Nano Lett

Publisher American Chemical Society

Specialty Biotechnology

Date 2020 Feb 1

PMID 32003222

Citations 35

Authors

Yuhang Jiang

Qiao Lu

Yongheng Wang

Emily Xu

Alison Ho

Priya Singh

Yifei Wang

Zhaozhong Jiang

Fan Yang

Gregory T Tietjen

Peter Cresswell

W Mark Saltzman

Affiliations

Soon will be listed here.

Abstract

Endosomal escape is a key step for intracellular drug delivery of nucleic acids, but reliable and sensitive methods for its quantitation remain an unmet need. In order to rationally optimize the mRNA transfection efficiency of a library of polymeric materials, we designed a deactivated Renilla luciferase-derived molecular probe whose activity can be restored only in the cytosol. This probe can be coencapsulated with mRNA in the same delivery vehicle, thereby accurately measuring its endosomal escape efficiency. We examined a library of poly(amine--ester) (PACE) polymers with different end groups using this probe and observed a strong correlation between endosomal escape and transfection efficiency ( = 0.9334). In addition, we found that mRNA encapsulation efficiency and endosomal escape, but not uptake, were determinant factors for transfection efficiency. The polymers with high endosomal escape/transfection efficiency also showed good transfection efficiency , and mRNA expression was primarily observed in spleens after intravenous delivery. Together, our study suggests that the luciferase probe can be used as an effective tool to quantitate endosomal escape, which is essential for rational optimization of intracellular drug delivery systems.

Citing Articles

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