Development of Guanidinium-rich Protein Mimics for Efficient siRNA Delivery into Human T Cells.

Development of Guanidinium-rich Protein Mimics for Efficient siRNA Delivery into Human T Cells. Biomacromolecules. 2015 Aug 31; Authors: deRonde BM, Torres JA, Minter LM, Tew GN Abstract RNA interference is gaining attention as a means to explore new molecular pathways and for its potential as a therapeutic; however, its application in immortal and primary T cells is limited due to challenges with efficient delivery in these cells types. Herein, we report the development of guanidinium-rich protein transduction domain mimics (PTDMs) based on a ring-opening metathesis polymerization scaffold that delivers siRNA into Jurkat T cells and human peripheral blood mononuclear cells (hPBMCs). Homopolymer and block copolymer PTDMs with varying numbers of guanidinium moieties were designed and tested to assess the role of cationic charge content and polymer architecture in siRNA delivery. Delivery of fluorescently-labeled siRNA into Jurkat T cells illustrates that the optimal cationic charge content, 40 charges per polymer, leads to higher efficiencies, with block copolymers outperforming their homopolymer counterparts. PTDMs also outperformed commercial reagents commonly used for siRNA delivery applications. Select PTDM candidates were further screened to assess the role PTDM structure has on the delivery of biologically active siRNA into primary cells. Specifically, siRNA to hNOTCH1 was delivered to hPBMCs enabling 50-80% knockdown efficienci...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research