Nanochannel-Based Poration Drives Benign and Effective Nonviral Gene Delivery to Peripheral Nerve Tissue.

Autor: Moore JT; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA., Wier CG; Department of Neuroscience, The Ohio State University, Columbus, OH, 43210, USA., Lemmerman LR; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA., Ortega-Pineda L; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA., Dodd DJ; Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, 43210, USA., Lawrence WR; Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, 43210, USA., Duarte-Sanmiguel S; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA.; Department of Human Sciences, The Ohio State University, Columbus, OH, 43210, USA., Dathathreya K; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA., Diaz-Starokozheva L; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Harris HN; Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Sen CK; School of Medicine, Indiana University, Indianapolis, IN, 46202, USA., Valerio IL; Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA, 02114, USA., Higuita-Castro N; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA.; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Arnold WD; Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Kolb SJ; Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.; Department of Biological Chemistry and Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Gallego-Perez D; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA.; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
Jazyk: angličtina
Zdroj: Advanced biosystems [Adv Biosyst] 2020 Nov; Vol. 4 (11), pp. e2000157. Date of Electronic Publication: 2020 Sep 16.
DOI: 10.1002/adbi.202000157
Abstrakt: While gene and cell therapies have emerged as promising treatment strategies for various neurological conditions, heavy reliance on viral vectors can hamper widespread clinical implementation. Here, the use of tissue nanotransfection as a platform nanotechnology to drive nonviral gene delivery to nerve tissue via nanochannels, in an effective, controlled, and benign manner is explored. TNT facilitates plasmid DNA delivery to the sciatic nerve of mice in a voltage-dependent manner. Compared to standard bulk electroporation (BEP), impairment in toe-spread and pinprick response is not caused by TNT, and has limited to no impact on electrophysiological parameters. BEP, however, induces significant nerve damage and increases macrophage immunoreactivity. TNT is subsequently used to deliver vasculogenic cell therapies to crushed nerves via delivery of reprogramming factor genes Etv2, Foxc2, and Fli1 (EFF). The results indicate the TNT-based delivery of EFF in a sciatic nerve crush model leads to increased vascularity, reduced macrophage infiltration, and improved recovery in electrophysiological parameters compared to crushed nerves that are TNT-treated with sham/empty plasmids. Altogether, the results indicate that TNT can be a powerful platform nanotechnology for localized nonviral gene delivery to nerve tissue, in vivo, and the deployment of reprogramming-based cell therapies for nerve repair/regeneration.
(© 2020 Wiley-VCH GmbH.)
Databáze: MEDLINE
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