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 Dong; Xuefeng Li; Yifan Wang; Wen Jing Lu; Eman Bahrani; Ly James Lee; Lesheng Teng; Wen Jiang; Feng Lan; Betty Y.S. Kim; Andrew S. Lee

doi:10.1038/s41551-022-00989-w

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

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	887-900
Number of pages	14
Journal	Nature Biomedical Engineering
Volume	7
Issue number	7
DOIs	https://doi.org/10.1038/s41551-022-00989-w
State	Published - Jul 2023

ASJC Scopus subject areas

Biotechnology
Bioengineering
Medicine (miscellaneous)
Biomedical Engineering
Computer Science Applications

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You, Y., Tian, Y., Yang, Z., Shi, J., Kwak, K. J., Tong, Y., Estania, A. P., Cao, J., Hsu, W. H., Liu, Y., Chiang, C. L., Schrank, B. R., Huntoon, K., Lee, D. Y., Li, Z., Zhao, Y., Zhang, H., Gallup, T. D., Ha, J. H., ... Lee, A. S. (2023). Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen-replacement therapy. Nature Biomedical Engineering, 7(7), 887-900. https://doi.org/10.1038/s41551-022-00989-w

You, Y, Tian, Y, Yang, Z, Shi, J, Kwak, KJ, Tong, Y, Estania, AP, Cao, J, Hsu, WH, Liu, Y, Chiang, CL, Schrank, BR, Huntoon, K, Lee, DY, Li, Z, Zhao, Y, Zhang, H, Gallup, TD, Ha, JH, Dong, S, Li, X, Wang, Y, Lu, WJ, Bahrani, E, Lee, LJ, Teng, L, Jiang, W, Lan, F, Kim, BYS & Lee, AS 2023, 'Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen-replacement therapy', Nature Biomedical Engineering, vol. 7, no. 7, pp. 887-900. https://doi.org/10.1038/s41551-022-00989-w

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title = "Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen-replacement therapy",

abstract = "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.",

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

note = "Funding Information: We thank C. Wogan of the Division of Radiation Oncology, MD Anderson Cancer Center, for editorial assistance. Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature Limited.",

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doi = "10.1038/s41551-022-00989-w",

language = "English (US)",

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AU - Tong, Yuhao

AU - Estania, Andreanne Poppy

AU - Cao, Jianhong

AU - Hsu, Wei Hsiang

AU - Liu, Yutong

AU - Chiang, Chi Ling

AU - Schrank, Benjamin R.

AU - Huntoon, Kristin

AU - Lee, Dae Yong

AU - Li, Ziwei

AU - Zhao, Yarong

AU - Zhang, Huan

AU - Gallup, Thomas D.

AU - Ha, Jong Hoon

AU - Dong, Shiyan

AU - Li, Xuefeng

AU - Wang, Yifan

AU - Lu, Wen Jing

AU - Bahrani, Eman

AU - Lee, Ly James

AU - Teng, Lesheng

AU - Jiang, Wen

AU - Lan, Feng

AU - Kim, Betty Y.S.

AU - Lee, Andrew S.

N1 - Funding Information: We thank C. Wogan of the Division of Radiation Oncology, MD Anderson Cancer Center, for editorial assistance. Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature Limited.

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

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