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通过电穿孔增强DNA或RNA疫苗的递送

Enhanced Delivery of DNA or RNA Vaccines by Electroporation.

作者信息

Broderick Kate E, Humeau Laurent M

机构信息

Inovio Pharmaceuticals, 660 West Germantown Pike, Suite 110, Plymouth Meeting, PA, 19462, USA.

出版信息

Methods Mol Biol. 2017;1499:193-200. doi: 10.1007/978-1-4939-6481-9_12.

Abstract

Nucleic acid vaccines are a next-generation branch of vaccines which offer major benefits over their conventional protein, bacteria, or viral-based counterparts. However, to be effective in large mammals and humans, an enhancing delivery technology is required. Electroporation is a physical technique which results in improved delivery of large molecules through the cell membrane. In the case of plasmid DNA and mRNA, electroporation enhances both the uptake and expression of the delivered nucleic acids. The muscle is an attractive tissue for nucleic acid vaccination in a clinical setting due to the accessibility and abundance of the target tissue. Historical clinical studies of electroporation in the muscle have demonstrated the procedure to be generally well tolerated in patients. Previous studies have determined that optimized electroporation parameters (such as electrical field intensity, pulse length, pulse width and drug product formulation) majorly impact the efficiency of nucleic acid delivery. We provide an overview of DNA/RNA vaccination in the muscle of mice. Our results suggest that the technique is safe and effective and is highly applicable to a research setting as well as scalable to larger animals and humans.

摘要

核酸疫苗是疫苗的一个下一代分支,与传统的蛋白质、细菌或病毒疫苗相比具有重大优势。然而,要在大型哺乳动物和人类中发挥作用,需要一种增强递送技术。电穿孔是一种物理技术,可通过细胞膜改善大分子的递送。对于质粒DNA和mRNA,电穿孔可增强递送核酸的摄取和表达。由于目标组织易于获取且丰富,肌肉是临床环境中核酸疫苗接种的有吸引力的组织。肌肉电穿孔的历史临床研究表明,该程序在患者中通常耐受性良好。先前的研究已确定,优化的电穿孔参数(如电场强度、脉冲长度、脉冲宽度和药物产品配方)对核酸递送效率有重大影响。我们概述了小鼠肌肉中的DNA/RNA疫苗接种。我们的结果表明,该技术安全有效,高度适用于研究环境,并且可扩展到更大的动物和人类。

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