Imperial College London
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Dr Asha K. Patel

Faculty of Medicine, National Heart & Lung Institute

Lecturer in Cell & Gene Therapy
 
 
 
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Contact

 

asha.patel

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Patel:2019:10.1002/adma.201805116,
author = {Patel, AK and Kaczmarek, JC and Bose, S and Kauffman, KJ and Mir, F and Heartlein, MW and DeRosa, F and Langer, R and Anderson, DG},
doi = {10.1002/adma.201805116},
journal = {Advanced Materials},
pages = {1--7},
title = {Inhaled nanoformulated mRNA polyplexes for protein production in lung epithelium},
url = {http://dx.doi.org/10.1002/adma.201805116},
volume = {31},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Noninvasive aerosol inhalation is an established method of drug delivery to the lung, and remains a desirable route for nucleicacidbased therapeutics. In vitro transcribed (IVT) mRNA has broad therapeutic applicability as it permits temporal and dosedependent control of encoded protein expression. Inhaled delivery of IVTmRNA has not yet been demonstrated and requires development of safe and effective materials. To meet this need, hyperbranched poly(beta amino esters) (hPBAEs) are synthesized to enable nanoformulation of stable and concentrated polyplexes suitable for inhalation. This strategy achieves uniform distribution of luciferase mRNA throughout all five lobes of the lung and produces 101.2 ng g−1 of luciferase protein 24 h after inhalation of hPBAE polyplexes. Importantly, delivery is localized to the lung, and no luminescence is observed in other tissues. Furthermore, using an Ai14 reporter mouse model it is identified that 24.6% of the total lung epithelial cell population is transfected after a single dose. Repeat dosing of inhaled hPBAEmRNA generates consistent protein production in the lung, without local or systemic toxicity. The results indicate that nebulized delivery of IVTmRNA facilitated by hPBAE vectors may provide a clinically relevant delivery system to lung epithelium.
AU  - Patel,AK
AU  - Kaczmarek,JC
AU  - Bose,S
AU  - Kauffman,KJ
AU  - Mir,F
AU  - Heartlein,MW
AU  - DeRosa,F
AU  - Langer,R
AU  - Anderson,DG
DO  - 10.1002/adma.201805116
EP  - 7
PY  - 2019///
SN  - 0935-9648
SP  - 1
TI  - Inhaled nanoformulated mRNA polyplexes for protein production in lung epithelium
T2  - Advanced Materials
UR  - http://dx.doi.org/10.1002/adma.201805116
UR  - https://onlinelibrary.wiley.com/doi/full/10.1002/adma.201805116
UR  - http://hdl.handle.net/10044/1/66597
VL  - 31
ER  -
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