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:2020:10.1021/acsnano.0c00326,
author = {Blakney, AK and Zhu, Y and McKay, PF and Bouton, CR and Yeow, J and Tang, J and Hu, K and Samnuan, K and Grigsby, CL and Shattock, RJ and Stevens, MM},
doi = {10.1021/acsnano.0c00326},
journal = {ACS Nano},
pages = {5711--5727},
title = {Big is beautiful: enhanced saRNA delivery and immunogenicity by a higher molecular weight, bioreducible, cationic polymer},
url = {http://dx.doi.org/10.1021/acsnano.0c00326},
volume = {14},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Self-amplifying RNA (saRNA) vaccines are highly advantageous, as they result in enhanced protein expression compared to mRNA (mRNA), thus minimizing the required dose. However, previous delivery strategies were optimized for siRNA or mRNA and do not necessarily deliver saRNA efficiently due to structural differences of these RNAs, thus motivating the development of saRNA delivery platforms. Here, we engineer a bioreducible, linear, cationic polymer called “pABOL” for saRNA delivery and show that increasing its molecular weight enhances delivery both in vitro and in vivo. We demonstrate that pABOL enhances protein expression and cellular uptake via both intramuscular and intradermal injection compared to commercially available polymers in vivo and that intramuscular injection confers complete protection against influenza challenge. Due to the scalability of polymer synthesis and ease of formulation preparation, we anticipate that this polymer is highly clinically translatable as a delivery vehicle for saRNA for both vaccines and therapeutics.
AU  - Blakney,AK
AU  - Zhu,Y
AU  - McKay,PF
AU  - Bouton,CR
AU  - Yeow,J
AU  - Tang,J
AU  - Hu,K
AU  - Samnuan,K
AU  - Grigsby,CL
AU  - Shattock,RJ
AU  - Stevens,MM
DO  - 10.1021/acsnano.0c00326
EP  - 5727
PY  - 2020///
SN  - 1936-0851
SP  - 5711
TI  - Big is beautiful: enhanced saRNA delivery and immunogenicity by a higher molecular weight, bioreducible, cationic polymer
T2  - ACS Nano
UR  - http://dx.doi.org/10.1021/acsnano.0c00326
UR  - http://hdl.handle.net/10044/1/79290
VL  - 14
ER  -
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