Nanochannel‐Based Poration Drives Benign and Effective Nonviral Gene Delivery to Peripheral Nerve Tissue
Jordan MooreChristopher G. WierLuke R. LemmermanLilibeth Ortega‐PinedaDaniel DoddWilliam LawrenceSilvia Duarte‐SanmiguelKavya DathathreyaLudmila Diaz‐StarokozhevaHallie HarrisChandan K. SenIan L. ValerioNatalia Higuita‐CastroW. David ArnoldStephen J. KolbDaniel Gallego‐Perez
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Abstract 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.Keywords:
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Gene delivery, a process of introducing foreign functional nucleic acids into target cells, has proven to be a very promising tool for inducing specific gene expression in host cells. Many different technologies have been developed for efficient gene delivery. Among them, electroporation has been adopted in gene delivery for decades, and it is currently widely used for transfection of different types of cells. Despite of the success achieved by bulk electroporation (BEP) for gene delivery in vitro and in vivo, it has significant drawbacks such as unstable transfection efficacy and low cell viability. In recent years, there is an emerging interest in understanding how individual cell accepts and responds to exogenous gene materials using single cell based micro-/nano-electroporation (MEP/NEP) technologies. In this review, the authors provide an overview of the recent development of MEP/NEP and their advantages in gene delivery. Additionally, the future perspectives of gene delivery with the application of electroporation are discussed. Keywords: Electroporation, gene delivery, nano-electroporation, nanocarriers, microfluidics.
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