Novel Protein Transduction Domain Mimics as Nonviral Delivery Vectors for siRNA Targeting NOTCH1 in Primary Human T cells
Novel Protein Transduction Domain Mimics as Nonviral Delivery Vectors for siRNA Targeting NOTCH1 in Primary Human T cells
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DOI：
10.1038/mt.2012.209
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发表时间：
2013-01-01
影响因子：
12.4
通讯作者：
Tew, Gregory N.
中科院分区：
文献类型：
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作者：
Tezgel, A. Oezguel;Gonzalez-Perez, Gabriela;Tew, Gregory N.
RNA干扰技术最近被认为是一种强大的研究方法，也是一种潜在的治疗多种疾病的方法。然而，将小干扰RNA(SiRNA)输送到T细胞系和原代血细胞是非常具有挑战性的，因为它们对传统试剂的转染具有抵抗力。因此，对非病毒、高效和易于制备的载体的需求尚未得到满足，以便将siRNA输送到难以转化的细胞类型。在这里，我们报道了一种基于蛋白质转导结构域模拟物(PTDM)的新系统，该系统通过开环复分解聚合产生，用于在细胞内递送siRNA分子。基于PTDM的siRNA传递在Jurkat T细胞和人外周血单核细胞中诱导高效的NOTCH1敲除，而没有任何测量的毒性。此外，将siRNA运送到人外周血细胞中的NOTCH1可调节细胞增殖和T细胞向T(H)1细胞的分化。
RNA interference technology has recently been highlighted as a powerful research method as well as a potential therapeutic treatment for several diseases. However, the delivery of small interfering RNA (siRNA) into T cell lines and primary blood cells is exceedingly challenging, as they are resistant to transfection by conventional reagents. As a result, there is an unmet need for nonviral, efficient, and easily prepared carriers for siRNA delivery into hard-to-transfect cell types. Here, we report a novel system based on protein transduction domain mimics (PTDMs), generated by ring opening metathesis polymerization, for intracellular delivery of siRNA molecules. PTDM-based siRNA delivery induced efficient NOTCH1 knockdown in Jurkat T cells and human peripheral blood mononuclear cells without any measured toxicity. Furthermore, delivering siRNA to NOTCH1 in human peripheral blood cells modulated cell proliferation and differentiation of T cells into T(H)1 cells.