期刊
PHARMACEUTICS
卷 13, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics13060800
关键词
mRNA therapeutics; RNA engineering; mRNA delivery
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [20H04524, 18K03529, JP18K19901]
- Japan Agency for Medical Research and Development (AMED) [JP18ae0201009]
- Grants-in-Aid for Scientific Research [18K03529, 20H04524] Funding Source: KAKEN
This study suggests a cation-free mRNA delivery strategy by hybridization of PEGylated RNA oligonucleotides with mRNA, which improves mRNA nuclease stability and protein expression efficiency significantly.
Messenger RNA (mRNA) delivery strategies are required to protect biologically fragile mRNA from ribonuclease (RNase) attacks to achieve efficient therapeutic protein expression. To tackle this issue, most mRNA delivery systems have used cationic components, which form electrostatically driven complexes with mRNA and shield encapsulated mRNA strands. However, cationic materials interact with anionic biomacromolecules in physiological environments, which leads to unspecific reactions and toxicities. To circumvent this issue of cation-based approaches, herein, we propose a cation-free delivery strategy by hybridization of PEGylated RNA oligonucleotides with mRNA. The PEG strands on the mRNA sterically and electrostatically shielded the mRNA, improving mRNA nuclease stability 15-fold after serum incubation compared with unhybridized mRNA. Eventually, the PEGylated mRNA induced nearly 20-fold higher efficiency of reporter protein expression than unhybridized mRNA in cultured cells. This study provides a platform to establish a safe and efficient cation-free mRNA delivery system.
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