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Updated: Dec 10, 2025

Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
Bundling of mRNA strands inside polyion complexes improves mRNA delivery efficiency in vitro and in vivo
Kyoko Koji1, Naoto Yoshinaga1, Yuki Mochida2
1Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Abstract:
RNA nanotechnology has promise for developing mRNA carriers with enhanced physicochemical and functional properties. However, the potential synergy for mRNA delivery of RNA nanotechnology in cooperation with established carrier systems remains unknown. This study proposes a combinational system of RNA nanotechnology and mRNA polyplexes, by focusing on mRNA steric structure inside the polyplexes. Firstly, several mRNA strands are bundled through hybridization with RNA oligonucleotide crosslinkers to obtain tight mRNA structure, and then the bundled mRNA is mixed with poly(ethylene glycol) (PEG)-polycation block copolymers to prepare PEG-coated polyplex micelles (PMs). mRNA bundling results in highly condensed mRNA packaging inside PM core with dense PEG chains on the surface, thereby, improving PM stability against polyion exchange reaction and ribonuclease (RNase) attack. Importantly, such stabilization effects are attributed to bundled structure of mRNA rather than the increase in total mRNA amount encapsulated in the PMs, as encapsulation of long mRNA strands without bundling fails to improve PM stability. Consequently, PMs loading bundled mRNA exhibit enhanced stability in mouse blood circulation, and induce efficient protein expression in cultured cells and mouse brain.
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