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Updated: Mar 14, 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
In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation
Xiaoyi Dong1,2, Wei Yan1,2, Xinmiao Long3,4
1The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Central South University, Changsha, 410013, Hunan, China.
In vivo T-cell engineering offers a faster, scalable alternative to traditional cell therapies for cancer. This approach engineers T cells within the body, reducing costs and improving accessibility for various diseases.
Area of Science:
- Immunology
- Biotechnology
- Oncology
Background:
- Chimeric antigen receptor (CAR)-T cell therapy is effective for blood cancers but faces challenges in traditional ex vivo engineering.
- Ex vivo T-cell engineering is time-consuming, costly, and difficult to control.
- In vivo T-cell engineering emerges as a promising strategy to overcome these limitations.
Purpose of the Study:
- To review the technical development and applications of in vivo T-cell engineering.
- To focus on innovations in delivery systems for in vivo T-cell engineering.
- To analyze therapeutic candidates and their efficacy and safety profiles.
Main Methods:
- Review of viral vector platforms and RNA-based platforms for in vivo T-cell engineering.
- Analysis of delivery platforms for therapeutic candidates.
- Discussion of preclinical and clinical data on efficacy and safety.
Main Results:
- In vivo T-cell engineering reduces costs and increases scalability compared to ex vivo methods.
- Viral vector and RNA-based platforms show advancements in delivery systems.
- Therapeutic candidates demonstrate potential in animal models and clinical applications.
Conclusions:
- In vivo T-cell engineering presents immense therapeutic potential across various diseases.
- Challenges remain in solid tumor targeting, precise regulation, and manufacturing.
- Continued development of in vivo programming strategies is crucial for future cell therapies.
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