Theranostics 2018; 8(9):2361-2376. doi:10.7150/thno.23438

Research Paper

Efficient delivery of nucleic acid molecules into skin by combined use of microneedle roller and flexible interdigitated electroporation array

Dong Huang1*, Deyao Zhao1*, Xiaoxia Wang1, Chunhui Li2, Tongren Yang2, Lili Du1, Zewen Wei3, Qiang Cheng1, Huiqing Cao1, Zicai Liang1, Yuanyu Huang2✉#, Zhihong Li1✉

1. National Key Laboratory of Science and Technology on Micro/Nano Fabrication; Institute of Microelectronics; Institute of Molecular Medicine; Peking University, Beijing 100871, China
2. Advanced Research Institute of Multidisciplinary Science, and School of Life Science, Beijing Institute of Technology, Beijing 100081, China
3. National Center for Nanoscience and Technology, Beijing 100190, China
*These authors contributed equally
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Citation:
Huang D, Zhao D, Wang X, Li C, Yang T, Du L, Wei Z, Cheng Q, Cao H, Liang Z, Huang Y, Li Z. Efficient delivery of nucleic acid molecules into skin by combined use of microneedle roller and flexible interdigitated electroporation array. Theranostics 2018; 8(9):2361-2376. doi:10.7150/thno.23438. Available from https://www.thno.org/v08p2361.htm

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Abstract

Rationale: Delivery of nucleic acid molecules into skin remains a main obstacle for various types of gene therapy or vaccine applications. Here we propose a novel electroporation approach via combined use of a microneedle roller and a flexible interdigitated electroporation array (FIEA) for efficient delivery of DNA and siRNA into mouse skin.

Methods: Using micromachining technology, closely spaced gold electrodes were made on a pliable parylene substrate to form a patch-like electroporation array, which enabled close surface contact between the skin and electrodes. Pre-penetration of the skin with a microneedle roller resulted in the formation of microchannels in the skin, which played a role as liquid electrodes in the skin and provided a uniform and deep electric field in the tissue when pulse stimulation was applied by FIEA.

Results: Using this proposed method, gene (RFP) expression and siRNA transfection were successfully achieved in normal mice skin. Anti-SCD1 siRNA electroporated via this method mediated significant gene silencing in the skin. Moreover, electroporation assisted by the microneedle roller showed significant advantages over treatment with FIEA alone. This allowed nucleic acid transportation at low voltage, with ideal safety outcomes.

Principal conclusions: Hence, the proposed electroporation approach in this study constitutes a novel way for delivering siRNA and DNA, and even other nucleic acid molecules, to mouse skin in vivo, potentially supporting clinical application in the treatment of skin diseases or intradermal/subcutaneous vaccination.

Keywords: electroporation, siRNA delivery, gene therapy, flexible interdigitated electroporation array, microneedle roller