Abstract

mRNA delivery has shown high application value in the treatment of various diseases, but its effective delivery is still a major challenge at present. Herein, we propose a lantern-shaped flexible RNA origami for mRNA delivery. The origami is composed of a target mRNA scaffold and only two customized RGD-modified circular RNA staples, which can compress the mRNA into nanoscale and facilitate its endocytosis by cells. In parallel, the flexible structure of the lantern-shaped origami allows large regions of the mRNA to be exposed and translated, exhibiting a good balance between endocytosis and translation efficiency. The application of lantern-shaped flexible RNA origami in the context of the tumor suppressor gene, Smad4 in colorectal cancer models demonstrates promising potential for accurate manipulation of protein levels in in vitro and in vivo settings. This flexible origami strategy provides a competitive delivery method for mRNA-based therapies.

mRNA delivery has shown great potential in the treatment of various diseases. Here, the authors develop a lantern-shaped flexible origami for nanolization of single mRNA molecules and demonstrate efficient delivery of Smad4 mRNA, achieving suppression of colorectal cancer tumour growth.

Details

Title
Lantern-shaped flexible RNA origami for Smad4 mRNA delivery and growth suppression of colorectal cancer
Author
Hu, Muren 1 ; Feng, Chang 2 ; Yuan, Qianqin 3 ; Liu, Chenbin 3 ; Ge, Bujun 4   VIAFID ORCID Logo  ; Sun, Fenyong 3   VIAFID ORCID Logo  ; Zhu, Xiaoli 3   VIAFID ORCID Logo 

1  Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Department of Clinical Laboratory Medicine, Shanghai, P. R. China (GRID:grid.412538.9) (ISNI:0000 0004 0527 0050); School of Medicine, Tongji University, Department of General Surgery, Tongji Hospital, Shanghai, P. R. China (GRID:grid.24516.34) (ISNI:0000000123704535) 
2  School of Life Sciences, Shanghai University, Center for Molecular Recognition and Biosensing, Shanghai, P. R. China (GRID:grid.39436.3b) (ISNI:0000 0001 2323 5732) 
3  Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Department of Clinical Laboratory Medicine, Shanghai, P. R. China (GRID:grid.412538.9) (ISNI:0000 0004 0527 0050) 
4  School of Medicine, Tongji University, Department of General Surgery, Tongji Hospital, Shanghai, P. R. China (GRID:grid.24516.34) (ISNI:0000000123704535) 
Pages
1307
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-023-37020-y
ProQuest document ID
2785038047
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.