Title | Novel protein transduction domain mimics as nonviral delivery vectors for siRNA targeting NOTCH1 in primary human T cells. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | A Tezgel, Ö, Gonzalez-Perez, G, Telfer, JC, Osborne, BA, Minter, LM, Tew, GN |
Journal | Mol Ther |
Volume | 21 |
Issue | 1 |
Pagination | 201-9 |
Date Published | 2013 Jan |
Keywords | CD4-Positive T-Lymphocytes, Cell Differentiation, Gene Knockdown Techniques, Humans, Jurkat Cells, Receptor, Notch1, RNA Interference, RNA, Small Interfering, Transduction, Genetic |
Abstract | 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. |
Alternate Journal | Mol. Ther. |
Veterinary and Animal Sciences