Issue 3, 2019

Identifying key barriers in cationic polymer gene delivery to human T cells

Abstract

T cells have emerged as a therapeutically-relevant target for ex vivo gene delivery and editing. However, most commercially available reagents cannot transfect T cells and designing cationic polymers for non-viral gene delivery to T cells has resulted in moderate success. Here, we assess various barriers to successful gene transfer in the Jurkat human T cell line and primary human T cells. Using two polymers previously developed by our group, we show that uptake is one barrier to gene delivery in primary human T cells but is not predictive of successful gene delivery. We then probe intracellular pathways for barriers to gene transfer including endosomal acidification, autophagy, and immune sensing pathways. We find that endosomal acidification is slower and not as robust in human T cells compared to the model HeLa human cell line commonly used to evaluate cationic polymers for gene delivery. These studies inform the future design of cationic polymers for non-viral gene delivery to T cells, specifically, to rely on alternative endosomal release mechanisms rather than on pH-triggered release.

Graphical abstract: Identifying key barriers in cationic polymer gene delivery to human T cells

Supplementary files

Article information

Article type
Paper
Submitted
09 Mph 2018
Accepted
19 Tsh 2018
First published
20 Tsh 2018

Biomater. Sci., 2019,7, 789-797

Identifying key barriers in cationic polymer gene delivery to human T cells

B. R. Olden, E. Cheng, Y. Cheng and S. H. Pun, Biomater. Sci., 2019, 7, 789 DOI: 10.1039/C8BM01262H

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