Big Is Beautiful: Enhanced saRNA Delivery and Immunogenicity by a Higher Molecular Weight, Bioreducible, Cationic Polymer
Open accessAbstract
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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In vivo experiments in mice showed that the delivery efficiency of pABOL is higher than that of PEI carriers.
“In addition, in vivo experiments in mice showed that the delivery efficiency of pABOL is higher than that of PEI carriers.”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [323]
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Self-citation
- Authors
- Blakney, A. K., Zhu, Y., McKay, P. F., Bouton, C. R., Yeow, J., Tang, J., Hu, K., Samnuan, K., Grigsby, C. L., Shattock, R. J., & Stevens, M. M.
- Affiliations
- Imperial College London (GB)
- Tongji University (CN)
- Imperial College London , , Norfolk Place , , ,
- Karolinska Institutet (SE)
- Corresponding author
- Shattock, Robin J.
- Stevens, Molly M.
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-04-08
- Volume
- 14
- Issue
- 5
- Pages
- 5711-5727
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- PMC
- PMC7304921
- OpenAlex
- W3014858505
- Cited by
- 155
- References
- 45
- Citations by year
- 2026: 11 · 2025: 24 · 2024: 35 · 2023: 22 · 2022: 26 · 2021: 27 · 2020: 10
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- ACS Nano (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- Horizon 2020 Framework Programme (794059)
- Medical Research Council (MR/R015651/1)
- Engineering and Physical Sciences Research Council (EP/R013764/1)
- Imperial College London (204834/Z/16/Z)
- Vetenskapsrådet (VR 4-478/2016)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- self-amplifying RNA vaccine, cationic polymers, bioreducible polymers, polymer molecular weight, immunogenicity, protein expression, cellular uptake, intramuscular injection, intradermal injection, influenza vaccination, vaccine adjuvants
- MeSH terms
- Cations, Molecular Weight, Polymers, RNA, Messenger, RNA, Small Interfering
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