Pseudovirions as vehicles for the delivery of siRNA.
Pseudovirions as vehicles for the delivery of siRNA.
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DOI：
10.1007/s11095-009-0012-2
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发表时间：
2010-03
影响因子：
3.7
通讯作者：
Kimchi-Sarfaty, Chava
中科院分区：
文献类型：
--
作者：
Lund, Paul E.;Hunt, Ryan C.;Gottesman, Michael M.;Kimchi-Sarfaty, Chava
在过去的二十年里，小干扰RNA(SiRNA)介导的基因沉默已迅速成为体外研究基因功能最强大的技术之一，并成为新疗法的一个有前途的领域。传递仍然是实现siRNA治疗潜力的重大障碍，这也是一个与免疫原性和毒性有关的问题。已经开发了许多递送载体，包括一些可被归类为假病毒子的载体：这些载体直接来自病毒，但其病毒编码序列已被消除，从而阻止了它们被归类为病毒载体。本文讨论的伪病毒粒子，即噬菌粒、单纯疱疹病毒扩增子、体外包装载体中的SV40、流感病毒小体和人类免疫缺陷病毒包膜载体的特点，使它们成为基于siRNA的治疗药物的载体。在体外和体内的免疫缺陷和免疫功能正常的小鼠模型中，假病毒粒子被证明能够传递siRNA效应分子并在不同类型的细胞中产生RNA干扰(RNAi)。沉默的水平并不总是直接确定的，但siRNA诱导的基因敲除持续时间至少为3天。我们列举了使用假病毒粒子传递合成的siRNA以及DNA导向的siRNA的传递和表达的例子。
Over the last two decades, small interfering RNA (siRNA)-mediated gene silencing has quickly become one of the most powerful techniques used to study gene function in vitro and a promising area for new therapeutics. Delivery remains a significant impediment to realizing the therapeutic potential of siRNA, a problem that is also tied to immunogenicity and toxicity. Numerous delivery vehicles have been developed including some that can be categorized as pseudovirions: these are vectors that are directly derived from viruses but whose viral coding sequences have been eliminated, preventing their classification as viral vectors. Characteristics of the pseudovirions discussed in this review, namely phagemids, HSV amplicons, SV40 in vitro-packaged vectors, influenza virosomes, and HVJ-Envelope vectors, make them attractive for the delivery of siRNA-based therapeutics. Pseudovirions were shown to deliver siRNA effector molecules and bring about RNA interference (RNAi) in various cell types in vitro, and in vivo using immune-deficient and immune-competent mouse models. Levels of silencing were not always determined directly, but the duration of siRNA-induced knockdown lasted at least 3 days. We present examples of the use of pseudovirions for the delivery of synthetic siRNA as well as the delivery and expression of DNA-directed siRNA.
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影响因子：
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作者：
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通讯作者：
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影响因子：
4.1
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