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Updated: Jun 26, 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
Non-viral vector-based genome editing for cancer immunotherapy
Tianxu Fang1,2, Guojun Chen1,2
1Department of Biomedical Engineering, McGill University, Montreal, QC, H3G 0B1, Canada. guojun.chen@mcgill.ca.
Abstract:
Despite the exciting promise of cancer immunotherapy in the clinic, immune checkpoint blockade therapy and T cell-based therapies are often associated with low response rates, intrinsic and adaptive immune resistance, and systemic side effects. CRISPR-Cas-based genome editing appears to be an effective strategy to overcome these unmet clinical needs. As a safer delivery platform for the CRISPR-Cas system, non-viral nanoformulations have been recently explored to target tumor cells and immune cells, aiming to improve cancer immunotherapy on a gene level. In this review, we summarized the efforts of non-viral vector-based CRISPR-Cas-mediated genome editing in tumor cells and immune cells for cancer immunotherapy. Their design rationale and specific applications were highlighted.
Insights
CRISPR-Cas genome editing using non-viral nanoformulations offers a promising strategy to enhance cancer immunotherapy by targeting tumor and immune cells. This approach aims to overcome low response rates and side effects associated with current treatments.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Immunology
Background:
- Cancer immunotherapy faces challenges like low response rates and immune resistance.
- CRISPR-Cas genome editing presents a potential solution for improving cancer treatments.
- Non-viral nanoformulations are being investigated as safer delivery systems for CRISPR-Cas.
Purpose of the Study:
- To review the application of non-viral vector-based CRISPR-Cas genome editing in cancer immunotherapy.
- To highlight the design rationale and specific applications of these systems.
- To explore their potential in overcoming current immunotherapy limitations.
Main Methods:
- Literature review of studies utilizing non-viral nanoformulations for CRISPR-Cas delivery.
- Analysis of CRISPR-Cas-mediated genome editing strategies targeting tumor and immune cells.
- Summarization of design principles and therapeutic applications.
Main Results:
- Non-viral nanoformulations enable targeted delivery of CRISPR-Cas systems to tumor and immune cells.
- Genome editing can enhance anti-tumor immune responses and reduce off-target effects.
- These strategies show promise in improving the efficacy and safety of cancer immunotherapy.
Conclusions:
- Non-viral vector-based CRISPR-Cas genome editing is a viable strategy to advance cancer immunotherapy.
- Targeted delivery and gene modulation offer a path to overcome resistance and side effects.
- Further research is warranted to optimize these systems for clinical translation.
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