首页> 外文期刊>Biochemical Pharmacology >Cationic liposomes as delivery systems for double-stranded PNA-DNA chimeras exhibiting decoy activity against NF-kappaB transcription factors.
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Cationic liposomes as delivery systems for double-stranded PNA-DNA chimeras exhibiting decoy activity against NF-kappaB transcription factors.

机译:阳离子脂质体作为双链PNA-DNA嵌合体的递送系统,对NF-κB转录因子表现出诱饵活性。

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摘要

Peptide nucleic acids (PNAs) have been recently proposed as useful molecules in pharmacogenetic therapy, especially due to the fact that they show a very high stability with respect to DNA and RNA. However, PNAs are not efficient decoy molecules, are characterized by negligible cell internalization and low solubility and are not suitable to be delivered by liposomes. With respect to the biological activity of PNA-based molecules, PDP deserve great consideration, due to the fact that they exhibit high levels of solubility, and are expected to be resistant to proteinases and exonucleases. In this manuscript we determined whether double-stranded molecules based on PNA-DNA chimeras containing NF-kappaB binding sites, exhibit decoy activity against NF-kappaB transcription factors. In addition, we determined whether they can be complexed by cationic liposomes. The results obtained demonstrated that hybrids based on PNA-DNA chimeras are powerful decoy molecules against NF-kappaB p52 transcription factor. In addition, we found that cationic liposomes can be proposed for in vitro delivery to target cells of these decoy molecules. The results presented in this paper are thus of practical importance, since the simplicity and the versatility of the cationic liposome technology have made cationic liposomes useful nonviral gene delivery systems for human gene therapy.
机译:肽核酸(PNA)最近被提出作为药物遗传学治疗中的有用分子,特别是由于它们对DNA和RNA表现出非常高的稳定性这一事实。然而,PNA不是有效的诱饵分子,其特征在于细胞内在化可忽略不计且溶解度低,并且不适合由脂质体递送。关于基于PNA的分子的生物学活性,由于PDP表现出高水平的溶解性,并且预期对蛋白酶和核酸外切酶具有抗性,因此值得深思。在这份手稿中,我们确定了基于PNA-DNA嵌合体的双链分子是否包含对NF-κB转录因子的诱饵活性。此外,我们确定了它们是否可以与阳离子脂质体复合。获得的结果表明,基于PNA-DNA嵌合体的杂种是抵抗NF-κBp52转录因子的强大诱饵分子。另外,我们发现阳离子脂质体可以被提议用于体外递送到这些诱饵分子的靶细胞。由于阳离子脂质体技术的简单性和多功能性已使阳离子脂质体成为用于人类基因治疗的非病毒基因递送系统,因此本文提出的结果具有实际意义。

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