期刊
ACS NANO
卷 14, 期 5, 页码 5711-5727出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c00326
关键词
RNA; replicon; polymer; vaccine; nucleic acid; influenza
类别
资金
- Whitaker Post-Doctoral Fellowship
- Marie Sklodowska Curie Individual Fellowship - European Commission H2020 [794059]
- UK Regenerative Medicine Platform Acellular/Smart Materials-3D Architecture [MR/R015651/1]
- Department of Health and Social Care (EPSRC) [EP/R013764/1]
- Imperial College London's Wellcome Trust Institutional Strategic Support Fund [204834/Z/16/Z]
- Swedish Research Council [VR 4-478/2016]
- Wellcome Trust [204834/Z/16/Z] Funding Source: Wellcome Trust
- EPSRC [EP/R013764/1] Funding Source: UKRI
- MRC [MR/R015651/1] Funding Source: UKRI
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.
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