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肽核酸的生物活性与生物技术方面

Biological activity and biotechnological aspects of peptide nucleic acid.

作者信息

Lundin Karin E, Good Liam, Strömberg Roger, Gräslund Astrid, Smith C I Edvard

机构信息

Department of Laboratory Medicine, Clinical Research Center Karolinska Institutet, Karolinska University Hospital, Huddinge 141 86 Stockholm, Sweden.

出版信息

Adv Genet. 2006;56:1-51. doi: 10.1016/S0065-2660(06)56001-8.

Abstract

During the latest decades a number of different nucleic acid analogs containing natural nucleobases on a modified backbone have been synthesized. An example of this is peptide nucleic acid (PNA), a DNA mimic with a noncyclic peptide-like backbone, which was first synthesized in 1991. Owing to its flexible and neutral backbone PNA displays very good hybridization properties also at low-ion concentrations and has subsequently attracted large interest both in biotechnology and biomedicine. Numerous modifications have been made, which could be of value for particular settings. However, the original PNA does so far perform well in many diverse applications. The high biostability makes it interesting for in vivo use, although the very limited diffusion over lipid membranes requires further modifications in order to make it suitable for treatment in eukaryotic cells. The possibility to use this nucleic acid analog for gene regulation and gene editing is discussed. Peptide nucleic acid is now also used for specific genetic detection in a number of diagnostic techniques, as well as for site-specific labeling and hybridization of functional molecules to both DNA and RNA, areas that are also discussed in this chapter.

摘要

在最近几十年里,人们合成了许多不同的核酸类似物,它们在修饰的主链上含有天然核碱基。其中一个例子是肽核酸(PNA),它是一种具有非环状肽样主链的DNA模拟物,于1991年首次合成。由于其主链具有柔韧性和中性,PNA在低离子浓度下也表现出非常好的杂交特性,随后在生物技术和生物医学领域引起了广泛关注。人们已经进行了许多修饰,这些修饰在特定情况下可能具有价值。然而,到目前为止,原始的PNA在许多不同的应用中表现良好。其高生物稳定性使其在体内应用方面具有吸引力,尽管其在脂质膜上的扩散非常有限,需要进一步修饰才能使其适用于真核细胞的治疗。本文讨论了使用这种核酸类似物进行基因调控和基因编辑的可能性。肽核酸现在还用于多种诊断技术中的特定基因检测,以及功能分子与DNA和RNA的位点特异性标记和杂交,本章也将讨论这些领域。

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