Imperial College London
Alternate

Dr Paul F. McKay

Faculty of Medicine, Department of Infectious Disease

Advanced Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2542p.mckay

 
 
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Location

 

125 (Shattock Group)Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Blakney:2021:10.1016/j.jconrel.2020.11.033,
author = {Blakney, A and Deletic, P and McKay, P and Bouton, C and Ashford, M and Shattock, R and Sabirsh, A},
doi = {10.1016/j.jconrel.2020.11.033},
journal = {Journal of Controlled Release},
pages = {1250--1261},
title = {Effect of complexing lipids on cellular uptake and expression of messengerRNA in human skin explants},
url = {http://dx.doi.org/10.1016/j.jconrel.2020.11.033},
volume = {330},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Messenger RNA (mRNA) represents a promising next-generation approach for both treatment and vaccination. Lipid based particles are one of the most investigated delivery systems for mRNA formulations. Here we explore how the complexing lipid affects uptake and translation of lipoplex-delivered RNA in resident cells in human skin explants and, we explore a more modular delivery system that utilizes mRNA added to pre-formed nanoparticles prior to dosing. We prepared formulations of lipoplexes with ionizable, cationic or zwitterionic lipids, externally complexed these with mRNA, and observed which cells internalized and/or expressed the mRNA over 72 h after intradermal injections into primary, human, skin explants. Using a flow cytometry panel to assess cellular phenotypes, mRNA uptake and mRNA expression, we found that, unlike other cell types, adipocytes expressed mRNA efficiently at 4 and 24 h after mRNA-lipoplex injection and contributed the greatest proportion of total RNA-encoded protein expression, despite being the lowest frequency cell type. Other cell types (epithelial cells, fibroblasts, T cells, B cells, dendritic cells, monocytes, NK cells, Langerhans cells, and leukocytes) had increasing mRNA expression over the course of 72 h, irrespective of lipoplex formulation. We observed that overall charge of the particle, but not the complexing lipid classification, was predictive for the pattern of mRNA uptake and expression among resident cell types in this model.This study provides insight into maximizing protein expression, using modular mRNA lipoplexes that are more compatible with product development, in a clinically relevant, human skin explant model.
AU  - Blakney,A
AU  - Deletic,P
AU  - McKay,P
AU  - Bouton,C
AU  - Ashford,M
AU  - Shattock,R
AU  - Sabirsh,A
DO  - 10.1016/j.jconrel.2020.11.033
EP  - 1261
PY  - 2021///
SN  - 0168-3659
SP  - 1250
TI  - Effect of complexing lipids on cellular uptake and expression of messengerRNA in human skin explants
T2  - Journal of Controlled Release
UR  - http://dx.doi.org/10.1016/j.jconrel.2020.11.033
UR  - http://hdl.handle.net/10044/1/85050
VL  - 330
ER  -
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