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Coalesced thermal and electrotransfer mediated delivery of plasmid DNA to the skin.
Bioelectrochemistry ( IF 5 ) Pub Date : 2018-10-23 , DOI: 10.1016/j.bioelechem.2018.10.004
Anna Bulysheva 1 , James Hornef 1 , Chelsea Edelblute 1 , Chunqi Jiang 1 , Karl Schoenbach 1 , Cathryn Lundberg 1 , Muhammad Arif Malik 1 , Richard Heller 2
Affiliation  

Efficient gene delivery and expression in the skin can be a promising minimally invasive technique for therapeutic clinical applications for immunotherapy, vaccinations, wound healing, cancer, and peripheral artery disease. One of the challenges for efficient gene electrotransfer (GET) to skin in vivo is confinement of expression to the epithelium. Another challenge involves tissue damage. Optimizing gene expression profiles, while minimizing tissue damage are necessary for therapeutic applications. Previously, we established that heating pretreatment to 43 °C enhances GET in vitro. We observed a similar trend in vivo, with an IR-pretreatment for skin heating prior to GET. Currently, we tested a range of GET conditions in vivo in guinea pigs with and without preheating the skin to ~43 °C. IR-laser heating and conduction heating were tested in conjunction with GET. In vivo electrotransfer to the skin by moderately elevating tissue temperature can lead to enhanced gene expression, as well as achieve gene transfer in epidermal, dermal, hypodermal and muscle tissue layers.



中文翻译:

结合的热和电转移介导质粒DNA向皮肤的递送。

皮肤中有效的基因传递和表达对于免疫疗法,疫苗接种,伤口愈合,癌症和外周动脉疾病的治疗性临床应用而言,可能是一种有前途的微创技术。在体内将有效基因电转移(GET)到皮肤的挑战之一是将表达限制在上皮细胞中。另一个挑战涉及组织损伤。对于治疗应用而言,优化基因表达谱,同时最大程度地减少组织损伤是必需的。以前,我们确定将预处理加热到43°C可以提高体外GET的水平。我们在体内观察到类似的趋势,即在GET之前使用IR预处理进行皮肤加热。目前,我们在体内测试了一系列GET条件在有或没有将皮肤预热到〜43°C的豚鼠中。结合GET测试了IR激光加热和传导加热。通过适度升高组织温度进行体内向皮肤的电转移可导致基因表达增强,以及在表皮,真皮,皮下和肌肉组织层中实现基因转移。

更新日期:2018-10-23
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