Polymer-based siRNA delivery: Perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery
Polymer-based siRNA delivery: Perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery
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DOI：
10.1016/j.jconrel.2007.05.021
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发表时间：
2007-08-16
影响因子：
10.8
通讯作者：
Won, You-Yeon
中科院分区：
文献类型：
--
作者：
Gary, Dana J.;Puri, Nitin;Won, You-Yeon
基因治疗在许多遗传性和获得性疾病的治疗中具有巨大的前景。然而，人类基因治疗的未来取决于安全有效的遗传物质载体的发现。聚合物代表了一类可以被广泛修饰以满足特定基因递送系统的需要的材料。在文献中已经提出了各种聚合物制剂作为潜在的载体，其中大多数通过包封促进基因递送，并且在某些情况下，将核酸浓缩成纳米尺寸的颗粒，然后可以被细胞吸收。将基因成功传递到细胞的关键是聚合物保护其内容物免受细胞外环境降解的能力。精心设计的载体还将促进核酸的细胞摄取和细胞内释放。过去，基因治疗的一种常见方法是用聚合物包裹的DNA质粒转染细胞，该质粒旨在取代靶细胞基因组中的缺陷基因。然而，在过去的几年里，RNA干扰（RNAi）已经成为一种新的治疗途径，通过它可以通过将互补的短干扰RNA（siRNA）传递到靶细胞来“沉默”有害基因。聚合物促进的SiRNA递送尽管非常有前途，但也受到许多与DNA递送相同的限制。这篇综述将（1）强调这两种基因治疗方法之间的相似性和差异，（2）讨论如何通过应用长期研究的DNA递送问题的知识来解决聚合物促进siRNA递送中的一些剩余挑战。(C)2007 Elsevier B.V.保留所有权利。
Gene therapy holds tremendous promise in the treatment of many genetic and acquired diseases. The future of gene therapy in humans, however, is contingent upon the discovery of safe and effective carriers of genetic material. Polymers represent a class of materials that can be extensively modified to meet the needs of a particular gene delivery system. A variety of polymer formulations have been proposed in the literature as potential carriers, most of which facilitate gene delivery by encapsulating, and in some cases, condensing nucleic acids into nano-sized particles which can then be taken up by cells. Crucial to successful delivery of the gene to a cell is the polymer's ability to protect its contents from degradation in the extracellular environment. A well-designed carrier will also promote cellular uptake and intracellular release of the nucleic acid. In the past, a common approach to gene therapy has been to transfect cells with a polymer-encapsulated DNA plasmid designed to replace a defective gene in the target-cell genome. Within the last few years, however, RNA interference (RNAi) has emerged as a novel therapeutic pathway by which harmful genes can be "silenced" by delivering complementary short interfering RNA (siRNA) to target cells. siRNA delivery facilitated by polymers, although very promising, suffers from many of the same limitations as DNA delivery. This review will (1) highlight the similarities and differences between these two methods of gene therapy and (2) discuss how some of the remaining challenges in siRNA delivery facilitated by polymers can be addressed by applying knowledge from the longer-studied problem of DNA delivery. (C) 2007 Elsevier B.V. All rights reserved.