Big is beautiful: enhanced saRNA delivery and immunogenicity by a higher molecular weight, bioreducible, cationic polymer
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Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2020-05-26
Date Acceptance
2020-04-08
Citation
ACS Nano, 2020, 14 (5), pp.5711-5727
ISSN
1936-0851
Publisher
American Chemical Society (ACS)
Start Page
5711
End Page
5727
Journal / Book Title
ACS Nano
Volume
14
Issue
5
Copyright Statement
© 2020 American Chemical Society. This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium,
provided the author and source are cited.
provided the author and source are cited.
Sponsor
Medical Research Council (MRC)
Engineering & Physical Science Research Council (EPSRC)
Commission of the European Communities
Wellcome Trust
Grant Number
MR/R015651/1
EP/R013764/1
794059
204834/Z/16/Z
Subjects
RNA
influenza
nucleic acid
polymer
replicon
vaccine
Nanoscience & Nanotechnology
Publication Status
Published
Article Number
acsnano.0c00326
Date Publish Online
2020-04-08