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

Yi You^#^{1

2}, Yu Tian^#^{1

2}, Zhaogang Yang^#^{3

4}, Junfeng Shi⁵, Kwang Joo Kwak⁵, Yuhao Tong^{1

2}, Andreanne Poppy Estania^{1

2}, Jianhong Cao^{1

2}, Wei-Hsiang Hsu^{1

2}, Yutong Liu^{1

2}, Chi-Ling Chiang⁶, Benjamin R Schrank³, Kristin Huntoon^{7

8}, DaeYong Lee^{7

8}, Ziwei Li⁴, Yarong Zhao⁴, Huan Zhang⁴, Thomas D Gallup^{7

8}, JongHoon Ha³, Shiyan Dong³, Xuefeng Li^{3

9}, Yifan Wang³, Wen-Jing Lu^{10

11}, Eman Bahrani¹², Ly James Lee⁵, Lesheng Teng⁴, Wen Jiang³, Feng Lan¹³, Betty Y S Kim^{14

15}, Andrew S Lee^{16

17}

Affiliations

¹ Peking University Shenzhen Graduate School, Shenzhen, China.
² Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, China.
³ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ School of Life Sciences, Jilin University, Changchun, China.
⁵ Spot Biosystems Ltd., Palo Alto, CA, USA.
⁶ Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
⁷ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, USA.
⁹ The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital; State Key Laboratory of Respiratory Disease, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
¹⁰ Fuwai Hospital Chinese Academy of Medical Sciences Shenzhen, Shenzhen Key Laboratory of Cardiovascular Disease, State Key Laboratory of Cardiovascular Disease and Peking Union Medical College, Shenzhen, China.
¹¹ Beijing Laboratory for Cardiovascular Precision Medicine, The Key Laboratory of Biomedical Engineering for Cardiovascular Disease Research, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
¹² Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA.
¹³ Fuwai Hospital Chinese Academy of Medical Sciences Shenzhen, Shenzhen Key Laboratory of Cardiovascular Disease, State Key Laboratory of Cardiovascular Disease and Peking Union Medical College, Shenzhen, China. Fenglan@fuwai.com.
¹⁴ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. bykim@mdanderson.org.
¹⁵ Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, USA. bykim@mdanderson.org.
¹⁶ Peking University Shenzhen Graduate School, Shenzhen, China. Alee@pku.edu.cn.
¹⁷ Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, China. Alee@pku.edu.cn.

^# Contributed equally.

PMID: 36635419
DOI: 10.1038/s41551-022-00989-w

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

Yi You et al. Nat Biomed Eng. 2023 Jul.

. 2023 Jul;7(7):887-900.

doi: 10.1038/s41551-022-00989-w. Epub 2023 Jan 12.

Authors

Affiliations

¹ Peking University Shenzhen Graduate School, Shenzhen, China.
² Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, China.
³ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ School of Life Sciences, Jilin University, Changchun, China.
⁵ Spot Biosystems Ltd., Palo Alto, CA, USA.
⁶ Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
⁷ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, USA.
⁹ The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital; State Key Laboratory of Respiratory Disease, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
¹⁰ Fuwai Hospital Chinese Academy of Medical Sciences Shenzhen, Shenzhen Key Laboratory of Cardiovascular Disease, State Key Laboratory of Cardiovascular Disease and Peking Union Medical College, Shenzhen, China.
¹¹ Beijing Laboratory for Cardiovascular Precision Medicine, The Key Laboratory of Biomedical Engineering for Cardiovascular Disease Research, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
¹² Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA.
¹³ Fuwai Hospital Chinese Academy of Medical Sciences Shenzhen, Shenzhen Key Laboratory of Cardiovascular Disease, State Key Laboratory of Cardiovascular Disease and Peking Union Medical College, Shenzhen, China. Fenglan@fuwai.com.
¹⁴ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. bykim@mdanderson.org.
¹⁵ Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, USA. bykim@mdanderson.org.
¹⁶ Peking University Shenzhen Graduate School, Shenzhen, China. Alee@pku.edu.cn.
¹⁷ Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, China. Alee@pku.edu.cn.

^# Contributed equally.

PMID: 36635419
DOI: 10.1038/s41551-022-00989-w

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.

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References

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

Affiliations

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

Authors

Affiliations

Abstract

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Miscellaneous