Genetically Stable and Scalable Nanoengineering of Human Primary T Cells via Cell Mechanoporation

Jeongsoo Hur, Hyelee Kim, Uijin Kim, Gi Beom Kim, Jinho Kim, Byeongju Joo, Duck Cho, Dong Sung Lee, Aram J. Chung

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Effective tumor regression has been observed with chimeric antigen receptor (CAR) T cells; however, the development of an affordable, safe, and effective CAR-T cell treatment remains a challenge. One of the major obstacles is that the suboptimal genetic modification of T cells reduces their yield and antitumor activity, necessitating the development of a next-generation T cell engineering approach. In this study, we developed a nonviral T cell nanoengineering system that allows highly efficient delivery of diverse functional nanomaterials into primary human T cells in a genetically stable and scalable manner. Our platform leverages the unique cell deformation and restoration process induced by the intrinsic inertial flow in a microchannel to create nanopores in the cellular membrane for macromolecule internalization, leading to effective transfection with high scalability and viability. The proposed approach demonstrates considerable potential as a practical alternative technique for improving the current CAR-T cell manufacturing process.

Original languageEnglish
Pages (from-to)7341-7349
Number of pages9
JournalNano Letters
Volume23
Issue number16
DOIs
StatePublished - 23 Aug 2023

Keywords

  • T cell engineering
  • hydroporator
  • immunoengineering
  • intracellular delivery
  • nonviral transfection

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