Mannosylated Poly(ethylene imine) Copolymers Enhance saRNA Uptake and Expression in Human Skin Explants.,Biomacromolecules

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Mannosylated Poly(ethylene imine) Copolymers Enhance saRNA Uptake and Expression in Human Skin Explants.
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-04-06 , DOI: 10.1021/acs.biomac.0c00445
Anna K Blakney ₁ , Yamin Abdouni ₂ , Gokhan Yilmaz ₃ , Renjie Liu ₂ , Paul F McKay ₁ , Clément R Bouton ₁ , Robin J Shattock ₁ , C Remzi Becer _{2,

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Affiliation

Messenger RNA (mRNA) is a promising platform for both vaccines and therapeutics, and self-amplifying RNA (saRNA) is particularly advantageous, as it enables higher protein expression and dose minimization. Here, we present a delivery platform for targeted delivery of saRNA using mannosylated poly(ethylene imine) (PEI) enabled by the host–guest interaction between cyclodextrin and adamantane. We show that the host–guest complexation does not interfere with the electrostatic interaction with saRNA and observed that increasing the degree of mannosylation inhibited transfection efficiency in vitro, but enhanced the number of cells expressing GFP by 8-fold in human skin explants. Besides, increasing the ratio of glycopolymer to saRNA also enhanced the percentage of transfected cells ex vivo. We identified that these mannosylated PEIs specifically increased protein expression in the epithelial cells resident in human skin in a mannose-dependent manner. This platform is promising for further study of glycosylation of PEI and targeted saRNA delivery.

中文翻译：

甘露糖基化的聚乙烯亚胺共聚物增强了人类皮肤植株中saRNA的吸收和表达。

Messenger RNA（mRNA）是用于疫苗和治疗剂的有前途的平台，自扩增RNA（saRNA）特别有利，因为它可以实现更高的蛋白表达和最小剂量。在这里，我们介绍了一个通过甘露糖基化的聚亚乙基亚胺（PEI）定向递送saRNA的递送平台，该环化糊精和金刚烷之间的客体相互作用实现了该平台。我们发现宿主-客体的复合物不会干扰与saRNA的静电相互作用，并且观察到甘露糖基化程度的提高在体外抑制了转染效率，但在人皮肤外植体中表达GFP的细胞数量增加了8倍。此外，提高糖聚合物与saRNA的比例也提高了离体转染细胞的百分比。我们发现，这些甘露糖基化的PEIs以依赖于甘露糖的方式特异性地增加了人类皮肤中上皮细胞的蛋白质表达。该平台有望用于进一步研究PEI的糖基化和靶向saRNA的传递。

更新日期：2020-04-06

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