Liposomes as carriers for DNA-PNA hybrids

Liposomes as carriers for DNA-PNA hybrids
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DOI:
10.1016/s0168-3659(00)00273-x
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发表时间:
2000-08-10
影响因子:
10.8
通讯作者:
Mischiati, C
Mischiati, C
中科院分区:
医学1区
文献类型:
--
作者:
Nastruzzi, C;Cortesi, R;Mischiati, C

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肽核酸 (PNA) 是由 N-(2-氨乙基)甘氨酸单元组成的 DNA 模拟物。这种结构赋予 PNA (a) 对 DNA 酶和蛋白酶的抗性。 (b) 以高亲和力与单链 RNA 和 DNA 的互补序列杂交的能力,以及 (c) 与 RNA 靶标形成高度稳定的 (PNA)(2)-RNA 三链体的能力。此外,DNA-PNA 杂合分子能够与 DNA 结合蛋白可逆地相互作用,因此对于通过诱饵方法调控基因表达的研究很有意义。本文的主要结论是阳离子脂质体能够有效地复合DNA-PNA杂化分子并介导它们与靶细胞的结合。我们的结果很有趣,因为与常用的核酸类似物不同,PNA 寡聚物不会自发地被细胞吸收。此外,它们: 不适合用常用的脂质体制剂进行有效递送。将 PNA-DNA 杂合分子转染到体外培养的细胞中对于确定这些新试剂在基因表达实验改变中的应用可能非常有意义。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Peptide nucleic acids (PNAs) are DNA mimics composed of N-(2-aminoethyl)glycine units. This structure gives to PNAs (a) resistance to DNases and proteinases. (b) capacity to hybridize with high affinity to complementary sequences of single-stranded RNA and DNA, and (c) capacity to form highly stable (PNA)(2)-RNA triplexes with RNA targets. Furthermore, DNA-PNA hybrid molecules are capable to reversibly interact with DNA-binding proteins, being therefore of interest for studies on regulation of gene expression by the decoy approach. The major conclusion of this paper is that cationic liposomes are able to efficiently complexate DNA-PNA hybrid molecules and mediate their binding to target cells. Our results are of some interest, since, unlike commonly used nucleic acids analogs, PNA oligomers are not taken up spontaneously into the cells. In addition, they are: not suitable for an efficient delivery with commonly used liposomal formulations. Transfection of PNA-DNA hybrid molecules to in vitro cultured cells could be of great interest to determine the applications of these new reagents to experimental alteration of gene expression. (C) 2000 Elsevier Science B.V. All rights reserved.