Imperial College London
Alternate

Professor Molly Stevens

Faculty of Engineering, Department of Materials

Professor of Biomedical Materials and Regenerative Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6804m.stevens

 
 
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Location

 

208Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Blakney:2021:10.1016/j.jconrel.2021.08.029,
author = {Blakney, AK and McKay, PF and Hu, K and Samnuan, K and Jain, N and Brown, A and Thomas, A and Rogers, P and Polra, K and Sallah, H and Yeow, J and Zhu, Y and Stevens, MM and Geall, A and Shattock, RJ},
doi = {10.1016/j.jconrel.2021.08.029},
journal = {Journal of Controlled Release},
pages = {201--210},
title = {Polymeric and lipid nanoparticles for delivery of self-amplifying RNA vaccines},
url = {http://dx.doi.org/10.1016/j.jconrel.2021.08.029},
volume = {338},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Self-amplifying RNA (saRNA) is a next-generation vaccine platform, but like all nucleic acids, requires a delivery vehicle to promote cellular uptake and protect the saRNA from degradation. To date, delivery platforms for saRNA have included lipid nanoparticles (LNP), polyplexes and cationic nanoemulsions; of these LNP are the most clinically advanced with the recent FDA approval of COVID-19 based-modified mRNA vaccines. While the effect of RNA on vaccine immunogenicity is well studied, the role of biomaterials in saRNA vaccine effectiveness is under investigated. Here, we tested saRNA formulated with either pABOL, a bioreducible polymer, or LNP, and characterized the protein expression and vaccine immunogenicity of both platforms. We observed that pABOL-formulated saRNA resulted in a higher magnitude of protein expression, but that the LNP formulations were overall more immunogenic. Furthermore, we observed that both the helper phospholipid and route of administration (intramuscular versus intranasal) of LNP impacted the vaccine immunogenicity of two model antigens (influenza hemagglutinin and SARS-CoV-2 spike protein). We observed that LNP administered intramuscularly, but not pABOL or LNP administered intranasally, resulted in increased acute interleukin-6 expression after vaccination. Overall, these results indicate that delivery systems and routes of administration may fulfill different delivery niches within the field of saRNA genetic medicines.
AU  - Blakney,AK
AU  - McKay,PF
AU  - Hu,K
AU  - Samnuan,K
AU  - Jain,N
AU  - Brown,A
AU  - Thomas,A
AU  - Rogers,P
AU  - Polra,K
AU  - Sallah,H
AU  - Yeow,J
AU  - Zhu,Y
AU  - Stevens,MM
AU  - Geall,A
AU  - Shattock,RJ
DO  - 10.1016/j.jconrel.2021.08.029
EP  - 210
PY  - 2021///
SN  - 0168-3659
SP  - 201
TI  - Polymeric and lipid nanoparticles for delivery of self-amplifying RNA vaccines
T2  - Journal of Controlled Release
UR  - http://dx.doi.org/10.1016/j.jconrel.2021.08.029
UR  - https://www.sciencedirect.com/science/article/pii/S0168365921004351?via%3Dihub
UR  - http://hdl.handle.net/10044/1/91260
VL  - 338
ER  -
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