Montazersaheb Soheila, Hejazi Mohammad Saeid, Nozad Charoudeh Hojjatollah
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Adv Pharm Bull. 2018 Nov;8(4):551-563. doi: 10.15171/apb.2018.064. Epub 2018 Nov 29.
Peptide nucleic acids (PNA) are synthetic analog of DNA with a repeating N-(2-aminoethyl)-glycine peptide backbone connected to purine and pyrimidine nucleobases via a linker. Considering the unique properties of PNA, including resistance to enzymatic digestion, higher biostability combined with great hybridization affinity toward DNA and RNA, it has attracted great attention toward PNA- based technology as a promising approach for gene alteration. However, an important challenge in utilizing PNA is poor intracellular uptake. Therefore, some strategies have been developed to enhance the delivery of PNA in order to reach cognate site. Although PNAs primarily demonstrated to act as an antisense and antigene agents for inhibition of transcription and translation of target genes, more therapeutic applications such as splicing modulation and gene editing are also used to produce specific genome modifications. Hence, several approaches based on PNAs technology have been designed for these purposes. This review briefly presents the properties and characteristics of PNA as well as different gene modulation mechanisms. Thereafter, current status of successful therapeutic applications of PNA as gene therapeutic intervention in different research areas with special interest in medical application in particular, anti-cancer therapy are discussed. Then it focuses on possible use of PNA as anti-mir agent and PNA-based strategies against clinically important bacteria.
肽核酸(PNA)是DNA的合成类似物,其具有通过连接子连接到嘌呤和嘧啶核碱基的重复N-(2-氨基乙基)-甘氨酸肽主链。鉴于PNA的独特性质,包括对酶消化的抗性、更高的生物稳定性以及对DNA和RNA的高杂交亲和力,基于PNA的技术作为一种有前景的基因改变方法已引起了极大关注。然而,利用PNA的一个重要挑战是细胞内摄取较差。因此,已经开发了一些策略来增强PNA的递送以到达同源位点。尽管PNA主要被证明可作为反义剂和反基因剂来抑制靶基因的转录和翻译,但诸如剪接调节和基因编辑等更多治疗应用也被用于产生特定的基因组修饰。因此,已经为这些目的设计了几种基于PNA技术的方法。本综述简要介绍了PNA的性质和特征以及不同的基因调节机制。此后,讨论了PNA作为基因治疗干预在不同研究领域,特别是在医学应用中,尤其是抗癌治疗方面成功治疗应用的现状。然后重点介绍了PNA作为抗miR剂的可能用途以及基于PNA的针对临床上重要细菌的策略。