Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen-replacement therapy

Yi You, Yu Tian, Zhaogang Yang, Junfeng Shi, Kwang Joo Kwak, Yuhao Tong, Andreanne Poppy Estania, Jianhong Cao, Wei Hsiang Hsu, Yutong Liu, Chi Ling Chiang, Benjamin R. Schrank, Kristin Huntoon, Dae Yong Lee, Ziwei Li, Yarong Zhao, Huan Zhang, Thomas D. Gallup, Jong Hoon Ha, Shiyan DongXuefeng Li, Yifan Wang, Wen Jing Lu, Eman Bahrani, Ly James Lee, Lesheng Teng, Wen Jiang, Feng Lan*, Betty Y.S. Kim*, Andrew S. Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The success of messenger RNA therapeutics largely depends on the availability of delivery systems that enable the safe, effective and stable translation of genetic material into functional proteins. Here we show that extracellular vesicles (EVs) produced via cellular nanoporation from human dermal fibroblasts, and encapsulating mRNA encoding for extracellular-matrix α1 type-I collagen (COL1A1) induced the formation of collagen-protein grafts and reduced wrinkle formation in the collagen-depleted dermal tissue of mice with photoaged skin. We also show that the intradermal delivery of the mRNA-loaded EVs via a microneedle array led to the prolonged and more uniform synthesis and replacement of collagen in the dermis of the animals. The intradermal delivery of EV-based COL1A1 mRNA may make for an effective protein-replacement therapy for the treatment of photoaged skin.

Original languageEnglish
JournalNature Biomedical Engineering
StateAccepted/In press - 2023


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