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Abstract：
Peptide nucleic acids (PNAs) are synthetic nucleic acid analogs with a neutral N-(2-aminoethyl) glycine backbone. PNAs possess unique physicochemical characteristics such as increased resistance to enzymatic degradation, ionic strength and stability over a wide range of temperatures and pH, and low intrinsic electrostatic repulsion against complementary target oligonucleotides. PNA has been widely used as an antisense oligonucleotide (ASO). Despite the favorable characteristics of PNA, in comparison with other ASO technologies, the use of antisense PNA for novel therapeutics has lagged. This review provides a brief overview of PNA, its antisense mechanisms of action, delivery strategies, and highlights successful applications of PNA, focusing on anti-pathogenic, anti-neurodegenerative disease, anti-cancer, and diagnostic agents. For each application, several studies are discussed focusing on the different target sites of the PNA, design of different PNAs and the therapeutic outcome in different cell lines and animal models. Thereafter, persisting limitations slowing the successful integration of antisense PNA therapeutics are discussed in order to highlight actionable next steps in the development and optimization of PNA as an ASO.
摘要：
肽核酸(PNA)是具有中性N-(2-氨基乙基)甘氨酸主链的合成核酸类似物。PNA具有独特的物理化学特性，例如对酶降解的抗性增加，在很宽的温度和pH范围内的离子强度和稳定性，和对互补靶寡核苷酸的低固有静电排斥。PNA已被广泛用作反义寡核苷酸(ASO)。尽管PNA具有良好的特性，与其他ASO技术相比，反义PNA在新疗法中的应用已经滞后。这篇综述简要概述了PNA，它的反义作用机制，交付策略，并强调了PNA的成功应用，专注于抗致病性，抗神经退行性疾病，抗癌，和诊断剂。对于每个应用程序，讨论了几项研究，重点是PNA的不同靶位点，不同PNA的设计以及在不同细胞系和动物模型中的治疗结果。此后,讨论了持续的局限性，这些局限性减缓了反义PNA疗法的成功整合，以强调PNA作为ASO的开发和优化中可行的后续步骤。
