TLR9-Targeted SiRNA Delivery In Vivo
TLR9-Targeted SiRNA Delivery In Vivo
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DOI：
10.1007/978-1-4939-3112-5_15
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
Kortylewski, Marcin
中科院分区：
文献类型：
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作者：
Hossain, Dewan Md Sakib;Moreira, Dayson;Kortylewski, Marcin
SiRNA策略是一种有效且通用的方法，用于调节各种物种中任何基因的表达以用于研究或治疗目的。基于siRNA的方法的临床转化被证明是具有挑战性的，主要是由于靶向siRNA递送到感兴趣的细胞中的困难和寡核苷酸试剂的免疫原性副作用。然而，免疫细胞对核酸的固有敏感性可用于递送设计用于癌症免疫治疗目的的SiRNA。我们已经证明，细胞内受体TLR 9的合成配体可以作为siRNA的细胞特异性递送的靶向部分。化学合成的CpG-SiRNA缀合物在不存在转染试剂的情况下被TLR 9阳性细胞快速内化，诱导靶基因沉默。CpG-SiRNA策略允许在将这些寡核苷酸局部或全身施用到小鼠中后在体内有效靶向TLR 9阳性细胞。
The SiRNA strategy is a potent and versatile method for modulating expression of any gene in various species for investigational or therapeutic purposes. Clinical translation of SiRNA-based approaches proved challenging, mainly due to the difficulty of targeted SiRNA delivery into cells of interest and the immunogenic side effects of oligonucleotide reagents. However, the intrinsic sensitivity of immune cells to nucleic acids can be utilized for the delivery of SiRNAs designed for the purpose of cancer immunotherapy. We have demonstrated that synthetic ligands for the intracellular receptor TLR9 can serve as targeting moiety for cell-specific delivery of SiRNAs. Chemically synthesized CpG-SiRNA conjugates are quickly internalized by TLR9-positive cells in the absence of transfection reagents, inducing target gene silencing. The CpG-SiRNA strategy allows for effective targeting of TLR9-positive cells in vivo after local or systemic administration of these oligonucleotides into mice.