ArticleNature biomedical engineering2024
Cas9-induced targeted integration of large DNA payloads in primary human T cells via homology-mediated end-joining DNA repair.
Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- Validation and analysis of 12,000 AI-driven CAR-T designs in the Bits to Binders competition.Molecular systems biology · 2026Article
- From Delivery to Design: Site-Specific Genome Engineering for Next-Generation CAR T-Cell Therapy.Biomedicines · 2026Review
- Progress in the development of cytokine armoured CAR T cells.Nature reviews. Immunology · 2026Review
- Efficient, fratricide free non-viral engineering of CD70-targeted CAR NK cells for hematologic and solid tumor immunotherapy.Molecular therapy. Advances · 2026Article
- Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Non-viral targeted integration of large DNA in primary human T cells independent of double-stranded DNA breaks.Nature biomedical engineering · 2026Article
- Ultra-large targeted DNA integrations in primary human cells.bioRxiv : the preprint server for biology · 2026Article
- CRISPR/Cas9 in cancer therapy: clinical translation, mechanistic strategies, and therapeutic directions.Frontiers in oncology · 2026Review
- Repurposing clinically safe drugs for DNA repair pathway choice in CRISPR genome editing and synthetic lethality.Nature communications · 2025Article
- Efficient high-precision transgene knock-in by Recombinases (Redα/β)-enhanced DNA integration-CRISPR-Cas9 (RED-CRISPR).Nature communications · 2025Article
- CRISPR tools for T cells: targeting the genome, epigenome, and transcriptome.Trends in cancer · 2025Review
- Single-stranded HDR templates with truncated Cas12a-binding sequences improve knock-in efficiencies in primary human T cells.Molecular therapy. Nucleic acids · 2025Article
- Efficient nonviral integration of large transgenes into human T cells using Cas9-CLIPT.Molecular therapy. Methods & clinical development · 2025Article
- Non-viral targeted insertion of large payloads into T cells.Nature biomedical engineering · 2024Article
- Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.bioRxiv : the preprint server for biology · 2024Article
- Metabolic priming of GD2Molecular therapy. Methods & clinical development · 2024Article
- Development and testing of a versatile genome editing application reporter (V-GEAR) system.Molecular therapy. Methods & clinical development · 2024Article
- Evolution of the clinical-stage hyperactive TcBuster transposase as a platform for robust non-viral production of adoptive cellular therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Strategies for Improved pDNA Loading and Protection Using Cationic and Neutral LNPs with Industrial Scalability Potential Using Microfluidic Technology.International journal of nanomedicine · 2024Article
- Non-viral expression of chimeric antigen receptors with multiplex gene editing in primary T cells.Frontiers in bioengineering and biotechnology · 2024Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
The reliance on viral vectors for the production of genetically engineered immune cells for adoptive cellular therapies remains a translational bottleneck. Here we report a method leveraging the DNA repair pathway homology-mediated end joining, as well as optimized reagent composition and delivery, for the Cas9-induced targeted integration of large DNA payloads into primary human T cells with low toxicity and at efficiencies nearing those of viral vectors (targeted knock-in of 1-6.7 kb payloads at rates of up to 70% at multiple targeted genomic loci and with cell viabilities of over 80%). We used the method to produce T cells with an engineered T-cell receptor or a chimaeric antigen receptor and show that the cells maintained low levels of exhaustion markers and excellent capacities for proliferation and cytokine production and that they elicited potent antitumour cytotoxicity in vitro and in mice. The method is readily adaptable to current good manufacturing practices and scale-up processes, and hence may be used as an alternative to viral vectors for the production of genetically engineered T cells for cancer immunotherapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.