Novel protein transduction domain mimics as nonviral delivery vectors for siRNA targeting NOTCH1 in primary human T cells.
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.
Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA.
A Özgül
AÖ
Tezgel
Gabriela
G
Gonzalez-Perez
Janice C
JC
Telfer
Barbara A
BA
Osborne
Lisa M
LM
Minter
Gregory N
GN
Tew
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D055785:Gene Knockdown Techniques; D006801:Humans; D019169:Jurkat Cells; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D051881:Receptor, Notch1 / Q000235:genetics*; D014161:Transduction, Genetic
C497761:NOTCH1 protein, human; D034741:RNA, Small Interfering; D051881:Receptor, Notch1