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Updated: Jan 12, 2026
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Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
Published on: May 9, 2025
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In vivo nano-engineering T cells for CAR-T therapy.
Tianyu Shi1, Yao Li2, Changchang Deng1
1Biomedical Polymers Laboratory, College of Chemistry Chemical Engineering and Materials Science and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, PR China.
Summary
In vivo nano-engineering enables building CAR T therapies within patients by integrating targeting, exposure, and expression. Spleen-targeting nanocarriers offer precise T-cell programming and immunomodulation.
Area of Science:
- Biotechnology
- Immunotherapy
- Nanomedicine
Background:
- In vivo nano-engineering of T cells is evolving beyond delivery to an integrated framework.
- Current approaches focus on targeting, exposure, and expression for CAR T therapies.
- Challenges include targeting precision, off-targeting, and batch consistency.
Purpose of the Study:
- To distill design rules for in vivo nano-engineering of T cells.
- To explore spleen-targeting nanocarriers as a novel therapeutic direction.
- To outline translational priorities for scalable, indication-tailored in vivo CAR T therapies.
Main Methods:
- Analysis of active targeting design rules on viral and nonviral carriers.
- Evaluation of spleen-tropic designs considering organ-scale factors.
- Investigation of payload logic for expression control.
Main Results:
- Active targeting design rules involve ligand architecture, avidity, and linker chemistry.
- Spleen-targeting nanocarriers offer selective delivery to T cell precursors.
- Specificity is achieved through payload logic, including tunable promoters and miRNA detargeting.
Conclusions:
- Coordinated design of active targeting, exposure, and expression control is crucial for in vivo CAR T therapies.
- Spleen-targeting nanocarriers represent a promising, underexplored therapeutic avenue.
- Translational priorities include enhancing targeting precision, analytics, and regulatory classification.
