Peptide nucleic acid (PNA) is arguably one of the most successful DNA mimics, despite a most dramatic departure from the native structure of DNA. The present review summarizes 30 years of research on PNA’s chemistry, optimization of structure and function, applications as probes and diagnostics, and attempts to develop new PNA therapeutics. The discussion starts with a brief review of PNA’s binding modes and structural features, followed by the most impactful chemical modifications, PNA enabled assays and diagnostics, and discussion of the current state of development of PNA therapeutics. While many modifications have improved on PNA’s binding affinity and specificity, solubility and other biophysical properties, the original PNA is still most frequently used in diagnostic and other in vitro applications. Development of therapeutics and other in vivo applications of PNA has notably lagged behind and is still limited by insufficient bioavailability and difficulties with tissue specific delivery. Relatively high doses are required to overcome poor cellular uptake and endosomal entrapment, which increases the risk of toxicity. These limitations remain unsolved problems waiting for innovative chemistry and biology to unlock the full potential of PNA in biomedical applications.

中文翻译：

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化学方法发现肽核酸在生物医学应用中的全部潜力


肽核酸 (PNA) 可以说是最成功的 DNA 模拟物之一，尽管它与 DNA 的天然结构有很大的不同。本综述总结了 30 年来对 PNA 化学、结构和功能优化、探针和诊断应用的研究，并尝试开发新的 PNA 疗法。讨论首先简要回顾 PNA 的结合模式和结构特征，然后是最有影响力的化学修饰、PNA 启用的检测和诊断，并讨论 PNA 疗法的当前发展状况。尽管许多修饰改进了 PNA 的结合亲和力和特异性、溶解度和其他生物物理特性，但原始 PNA 仍然最常用于诊断和其他体外应用。 PNA 的治疗方法和其他体内应用的开发明显滞后，并且仍然受到生物利用度不足和组织特异性递送困难的限制。需要相对较高的剂量来克服细胞摄取不良和内体截留，这增加了毒性风险。这些限制仍然是未解决的问题，等待创新的化学和生物学来释放 PNA 在生物医学应用中的全部潜力。