体内
免疫原性
信使核糖核酸
体外
材料科学
生物
基因
免疫系统
免疫学
生物化学
遗传学
作者
Anna K. Blakney,Yunqing Zhu,Paul F. McKay,Clément R. Bouton,Jonathan Yeow,Jiaqing Tang,Kai Hu,Karnyart Samnuan,Christopher L. Grigsby,Robin J. Shattock,Molly M. Stevens
出处
期刊:ACS Nano
[American Chemical Society]
日期:2020-04-08
卷期号:14 (5): 5711-5727
被引量:95
标识
DOI:10.1021/acsnano.0c00326
摘要
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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