Novel Protein Transduction Domain Mimics As Nonviral Delivery Vectors for SiRNA Targeting NOTCH1 in Primary Human T Cells

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2012 Oct 17

PMID 23070119

Citations 23

Authors

A Ozgul Tezgel

Gabriela Gonzalez-Perez

Janice C Telfer

Barbara A Osborne

Lisa M Minter

Gregory N Tew

Affiliations

Soon will be listed here.

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.

Citing Articles

Protein Transduction Domain Mimic (PTDM) Self-Assembly?.

Posey N, Tew G Polymers (Basel). 2019; 10(9).

PMID: 30960964 PMC: 6403535. DOI: 10.3390/polym10091039.

Enhanced mRNA delivery into lymphocytes enabled by lipid-varied libraries of charge-altering releasable transporters.

McKinlay C, Benner N, Haabeth O, Waymouth R, Wender P Proc Natl Acad Sci U S A. 2018; 115(26):E5859-E5866.

PMID: 29891683 PMC: 6042134. DOI: 10.1073/pnas.1805358115.

Effect of dihydroarteminin combined with siRNA targeting Notch1 on Notch1/c-Myc signaling in T-cell lymphoma cells.

Huo L, Wei W, Wu S, Zhao X, Zhao C, Zhao H Exp Ther Med. 2018; 15(3):3059-3065.

PMID: 29599840 PMC: 5867475. DOI: 10.3892/etm.2018.5784.

Increased Hydrophobic Block Length of PTDMs Promotes Protein Internalization.

Backlund C, Sgolastra F, Otter R, Minter L, Takeuchi T, Futaki S Polym Chem. 2017; 7(48):7514-7521.

PMID: 29093759 PMC: 5661863. DOI: 10.1039/C6PY01615D.

ROMP- and RAFT-Based Guanidinium-Containing Polymers as Scaffolds for Protein Mimic Synthesis.

Sarapas J, Backlund C, deRonde B, Minter L, Tew G Chemistry. 2017; 23(28):6858-6863.

PMID: 28370636 PMC: 5551038. DOI: 10.1002/chem.201700423.

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