Peptides used in the delivery of small noncoding RNA.
Peptides used in the delivery of small noncoding RNA.
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DOI：
10.1021/mp500426r
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发表时间：
2014-10-06
影响因子：
4.9
通讯作者：
Cheng K
中科院分区：
文献类型：
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作者：
Shukla RS;Qin B;Cheng K
RNA干扰（RNA interference，RNAi）是一种内源性的基因表达调控过程，由小分子非编码RNA（small noncoding RNA，siRNA）和微小RNA（microRNA，miRNAs）组成。通常，siRNA和miRNA/miRNA模拟物在性质和活性上相似，除了它们的来源和特异性。尽管siRNA和miRNA都已被广泛研究作为用于广泛疾病的新型治疗剂，但大分子量、阴离子表面电荷、血液循环中的不稳定性以及细胞摄取后向RISC的细胞内运输阻碍了这些RNA从实验室到临床的翻译。因此，已经研究了多种递送系统以安全有效地递送小的非编码RNA。在这些系统中，肽，特别是阳离子肽，由于其固有的能力，缩合带负电荷的RNA，易于合成，可控的大小，和可调的结构，已成为一种有前途的类型的载体。本文主要介绍了三种主要的阳离子多肽，包括聚赖氨酸（PLL）、鱼精蛋白和细胞穿透肽（CPP），以及广泛应用于RNA递送的肽靶向配体。这些阳离子肽在siRNA/miRNA递送中的递送策略、应用和限制将被讨论。
RNA interference (RNAi) is an endogenous process in which small noncoding RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs), post-transcriptionally regulate gene expressions. In general, siRNA and miRNA/miRNA mimics are similar in nature and activity except their origin and specificity. Although both siRNAs and miRNAs have been extensively studied as novel therapeutics for a wide range of diseases, the large molecular weight, anionic surface charges, instability in blood circulation, and intracellular trafficking to the RISC after cellular uptake have hindered the translation of these RNAs from bench to clinic. As a result, a great variety of delivery systems have been investigated for safe and effective delivery of small noncoding RNAs. Among these systems, peptides, especially cationic peptides, have emerged as a promising type of carrier due to their inherent ability to condense negatively charged RNAs, ease of synthesis, controllable size, and tunable structure. In this review, we will focus on three major types of cationic peptides, including poly(l-lysine) (PLL), protamine, and cell penetrating peptides (CPP), as well as peptide targeting ligands that have been extensively used in RNA delivery. The delivery strategies, applications, and limitations of these cationic peptides in siRNA/miRNA delivery will be discussed.
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