Novel Protein Transduction Domain Mimics as Nonviral Delivery Vectors for siRNA Targeting NOTCH1 in Primary Human T cells

作者：Tezgel A Oezguel; Gonzalez Perez Gabriela; Telfer Janice C; O**orne Barbara A; Minter Lisa M; Tew Gregory N^*

来源：Molecular Therapy, 2013, 21(1): 201-209.

DOI：10.1038/mt.2012.209

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.

• 出版日期2013-1