Cationic carriers of genetic material and cell death: A mitochondrial tale

Cationic carriers of genetic material and cell death: A mitochondrial tale
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DOI:
10.1016/j.bbabio.2010.03.026
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发表时间:
2010-06-01
影响因子:
4.3
通讯作者:
Moghimi, S. Moein
Moghimi, S. Moein
中科院分区:
生物学2区
文献类型:
--
作者:
Hunter, A. Christy;Moghimi, S. Moein

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基因治疗技术的核心是使用阳离子聚合物作为DNA和RNA的载体(多转染素)。据推测,这些系统比病毒系统更安全,例如,已经发现病毒系统可以启动致癌基因。已被深入研究用作合成载体的两种关键聚阳离子是聚(乙烯亚胺)和聚(L-赖氨酸)。一个常见的绊脚石与这些polyfectins是长期的基因表达细胞系尚未实现。最近发现这两种聚阳离子都能诱导神经细胞介导的细胞凋亡。这篇综述的目的是讨论所观察到的聚阳离子毒性背后的机制,包括在这个过程中很少研究的细胞器,如溶酶体和内质网的作用。(C)2010 Elsevier B. V.保留所有权利。
Central to gene therapy technology has been the use of cationic polymers as vectors for DNA and RNA (polyfectins). These have been presumed to be safer than viral systems which, for example, have been found to switch on oncogenes. Two key polycations that have been intensively researched for use as synthetic vectors are poly(ethylenimine) and poly(L-lysine). A frequent stumbling block with these polyfectins is that long-term gene expression in cell lines has not been achieved. Recently it has transpired that both of these polycations can induce mitochondrially mediated apoptosis. It is the aim of this review to discuss the mechanisms behind the observed polycation toxicity including roles for little studied cellular organelles in the process such as the lysosome and endoplasmic reticulum. (C) 2010 Elsevier B.V. All rights reserved.