Nanochannel-Based Poration Drives Benign and Effective Nonviral Gene Delivery to Peripheral Nerve Tissue.
Nanochannel-Based Poration Drives Benign and Effective Nonviral Gene Delivery to Peripheral Nerve Tissue.
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DOI：
10.1002/adbi.202000157
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发表时间：
2020-11
影响因子：
4.1
通讯作者：
Gallego-Perez D
中科院分区：
文献类型：
--
作者：
Moore JT;Wier CG;Lemmerman LR;Ortega-Pineda L;Dodd DJ;Lawrence WR;Duarte-Sanmiguel S;Dathathreya K;Diaz-Starokozheva L;Harris HN;Sen CK;Valerio IL;Higuita-Castro N;Arnold WD;Kolb SJ;Gallego-Perez D
虽然基因和细胞疗法已成为各种神经系统疾病的有前途的治疗策略，但对病毒载体的严重依赖可能会阻碍广泛的临床实施。在这里，我们探索了使用组织纳米转染（TNT）作为平台纳米技术，以有效，可控和良性的方式通过纳米通道驱动非病毒基因递送到神经组织。TNT以电压依赖性方式促进质粒DNA递送到小鼠坐骨神经。与标准批量电穿孔（BEP）相比，TNT不会导致脚趾伸展和针刺反应受损，并且对电生理参数的影响有限或没有影响。然而，BEP诱导显著的神经损伤和增加巨噬细胞免疫反应性。TNT随后被用于通过递送重编程因子基因Etv 2、Foxc 2和Fli 1（EFF）来向压碎的神经递送血管生成细胞疗法。我们的研究结果表明，在坐骨神经挤压模型中，与用假/空质粒TNT处理的挤压神经相比，基于TNT的EFF递送导致血管分布增加，巨噬细胞浸润减少，电生理参数恢复改善。总而言之，我们的研究结果表明，TNT可能是一种强大的平台纳米技术，用于在体内将非病毒基因递送到神经组织，以及部署基于重编程的细胞疗法用于神经修复/再生。
While gene and cell therapies have emerged as promising treatment strategies for various neurological conditions, heavy reliance on viral vectors could hamper widespread clinical implementation. Here, we explored the use of Tissue Nano-Transfection (TNT) as a platform nanotechnology to drive non-viral gene delivery to nerve tissue via nanochannels, in an effective, controlled, and benign manner. TNT facilitated plasmid DNA delivery to the sciatic nerve of mice in a voltage-dependent manner. Compared to standard bulk electroporation (BEP), TNT did not cause impairment in toe-spread and pinprick response, and had limited to no impact on electrophysiological parameters. BEP, however, induced significant nerve damage and increased macrophage immunoreactivity. TNT was subsequently used to deliver vasculogenic cell therapies to crushed nerves via delivery of reprogramming factor genes Etv2, Foxc2, and Fli1 (EFF). Our results indicate the TNT-based delivery of EFF in a sciatic nerve crush model led to increased vascularity, reduced macrophage infiltration, and improved recovery in electrophysiological parameters compared to crushed nerves that were TNT-treated with sham/empty plasmids. Altogether, our results indicate that TNT could be a powerful platform nanotechnology for localized non-viral gene delivery to nerve tissue, in vivo, and the deployment of reprogramming-based cell therapies for nerve repair/regeneration.
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影响因子：
2.6
作者：
Ecklund, James M.;Ling, Geoffrey S. F.
通讯作者：
Ling, Geoffrey S. F.
影响因子：
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Arai, Ken;Lo, Eng H.
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Lo, Eng H.
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38.3
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Gallego-Perez D;Pal D;Ghatak S;Malkoc V;Higuita-Castro N;Gnyawali S;Chang L;Liao WC;Shi J;Sinha M;Singh K;Steen E;Sunyecz A;Stewart R;Moore J;Ziebro T;Northcutt RG;Homsy M;Bertani P;Lu W;Roy S;Khanna S;Rink C;Sundaresan VB;Otero JJ;Lee LJ;Sen CK
通讯作者：
Sen CK
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4.4
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JACOBS, JM;RO, LS
通讯作者：
RO, LS
影响因子：
5.9
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Han JW;Sin MY;Yoon YS
通讯作者：
Yoon YS