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Updated: Dec 18, 2025

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
Published on: May 9, 2025
Gene delivery for immunoengineering
Sarah Y Neshat1, Stephany Y Tzeng1, Jordan J Green2
1Department of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Abstract:
A growing number of gene delivery strategies are being employed for immunoengineering in applications ranging from infectious disease prevention to cancer therapy. Viral vectors tend to have high gene transfer capability but may be hampered by complications related to their intrinsic immunogenicity. Non-viral methods of gene delivery, including polymeric, lipid-based, and inorganic nanoparticles as well as physical delivery techniques, have also been widely investigated. By using either ex vivo engineering of immune cells that are subsequently adoptively transferred or in vivo transfection of cells for in situ genetic programming, researchers have developed different approaches to precisely modulate immune responses. In addition to expressing a gene of interest through intracellular delivery of plasmid DNA and mRNA, researchers are also delivering oligonucleotides to knock down gene expression and immunostimulatory nucleic acids to tune immune activity. Many of these biotechnologies are now in clinical trials and have high potential to impact medicine.
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