Lantern-shaped flexible RNA origami for Smad4 mRNA delivery and growth suppression of colorectal cancer

Muren Hu, Chang Feng, Qianqin Yuan, Chenbin Liu, Bujun Ge (), Fenyong Sun () and Xiaoli Zhu ()
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Muren Hu: Shanghai Tenth People’s Hospital, School of Medicine, Tongji University
Chang Feng: School of Life Sciences, Shanghai University
Qianqin Yuan: Shanghai Tenth People’s Hospital, School of Medicine, Tongji University
Chenbin Liu: Shanghai Tenth People’s Hospital, School of Medicine, Tongji University
Bujun Ge: School of Medicine, Tongji University
Fenyong Sun: Shanghai Tenth People’s Hospital, School of Medicine, Tongji University
Xiaoli Zhu: Shanghai Tenth People’s Hospital, School of Medicine, Tongji University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37020-y

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