Genetic modification of T cells
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Updated: May 1, 2026

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
Published on: May 9, 2025
Richard A Morgan1, Sunitha Kakarla
1From Bluebird Bio, Cambridge, MA.R.A.M. and S.K. are employees of and own equity in Bluebird Bio.
Abstract:
Gene transfer technology has advanced rapidly from simple physical-chemical laboratory methods in the 1970s and 1980s to the sophisticated viral and nonviral methods currently in clinical practice. Herein, we review 4 gene transfer methodologies applied in human gene therapy clinical trials transferring chimeric antigen receptors into T cells for the treatment of B-cell malignancies. The 4 methods include 2 viral vector gene transfer technologies, gamma retroviral vectors and lentiviral vectors, and 2 nonviral methods, transposons and mRNA electroporation.
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