Electroporation, or the use of electric pulses to facilitate the intracellular delivery of DNA, RNA, and other molecules, is a well‐established technique, that has been demonstrated to significantly augment the immunogenicity of DNA/mRNA vaccines and therapeutics. However, the clinical translation of traditional electroporators has been limited due to high costs, large size, complex user operation, and poor tolerability in humans due to nerve stimulation. In prior work, we introduced ePatch: an ultra‐low‐cost, handheld, battery‐free electroporator employing a piezoelectric pulser coupled with a microneedle electrode array that showed enhanced immunogenic responses to an intradermal SARS‐CoV‐2 DNA vaccine in mice. The current study shifts focus from efficacy to tolerability, hypothesizing that ePatch's microneedle array, which localizes the electric field to the superficial skin strata, will minimize nerve stimulation and improve patient comfort. We tested this hypothesis in 14 healthy adults, monitoring pain and other potential adverse effects associated with electroporation. Compared to the insertion of a traditional hypodermic needle, the ePatch was less painful. Adverse effects such as pain, tenderness, erythema and swelling at the application sites were minimal, transient, and statistically indistinguishable between the experimental and placebo ePatch application, suggesting excellent tolerability towards electroporation. In summary, ePatch has a favorable tolerability profile in humans and offers the potential for the safe use of electroporation in a variety of clinical settings, including DNA and mRNA vaccination.

中文翻译：

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压电微针电穿孔器在人体中的耐受性

电穿孔或使用电脉冲促进 DNA、RNA 和其他分子的细胞内递送是一项成熟的技术，已被证明可以显着增强 DNA/mRNA 疫苗和治疗的免疫原性。然而，传统电穿孔仪的临床转化由于成本高、体积大、用户操作复杂以及神经刺激引起的人体耐受性差而受到限制。在之前的工作中，我们介绍了 ePatch：一种超低成本、手持式、无电池电穿孔器，采用压电脉冲发生器与微针电极阵列相结合，显示出对小鼠皮内 SARS-CoV-2 DNA 疫苗的增强的免疫原性反应。目前的研究将焦点从疗效转向耐受性，假设 ePatch 的微针阵列将电场定位到浅表皮肤层，将最大限度地减少神经刺激并提高患者舒适度。我们在 14 名健康成年人中测试了这一假设，监测与电穿孔相关的疼痛和其他潜在不良反应。与传统的皮下注射针插入相比，ePatch 的疼痛较小。实验性 ePatch 应用和安慰剂 ePatch 应用之间的不良反应（例如应用部位的疼痛、压痛、红斑和肿胀）是最小的、短暂的，并且在统计学上无法区分，这表明对电穿孔具有极好的耐受性。总之，ePatch 在人类中具有良好的耐受性，并为在各种临床环境中安全使用电穿孔提供了潜力，包括 DNA 和 mRNA 疫苗接种。