ArticleBlood2023
Novel extragenic genomic safe harbors for precise therapeutic T-cell engineering.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- From Delivery to Design: Site-Specific Genome Engineering for Next-Generation CAR T-Cell Therapy.Biomedicines · 2026Review
- Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Human Genome Safe Harbor Sites: A Comprehensive Review of Criteria, Discovery, Features, and Applications.Cells · 2026Review
- Development of evolutionarily conserved viral integration sites as safe harbors for human gene therapy.iScience · 2025Article
- Viral vector-free generation of orthogonal IL-2-responsive CAR T cells through gene editing of IL-2 and its receptor.Blood immunology & cellular therapy · 2025Article
- Preventing secondary primary malignancies (SPMs) in CAR-T cell therapy through site-specific transgene integration into genomic safe harbors (GSHs).Journal of translational medicine · 2025Review
- Turning "trashed" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Gene editing of CD3 epsilon to redirect regulatory T cells for adoptive T cell transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy.Leukemia · 2024Review
- Engineering immune-evasive allogeneic cellular immunotherapies.Nature reviews. Immunology · 2024Review
- The Current Landscape of Secondary Malignancies after CAR T-Cell Therapies: How Could Malignancies Be Prevented?International journal of molecular sciences · 2024Review
- The Fate(s) of CAR T-Cell Therapy: Navigating the Risks of CAR+ T-Cell Malignancy.Blood cancer discovery · 2024Review
- Integration of ζ-deficient CARs into the CD3ζ gene conveys potent cytotoxicity in T and NK cells.Blood · 2024Article
- CRISPR-Cas9 applications in T cells and adoptive T cell therapies.Cellular & molecular biology letters · 2024Review
- Answering the "Doctor, can CAR-T therapy cause cancer?" question in clinic.Blood advances · 2024Article
- CAR-T cell manufacturing: Major process parameters and next-generation strategies.The Journal of experimental medicine · 2024Review
- Article
- Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy (CAR-T) cell immunotherapy.Oncology research · 2024Review
- Challenges of CRISPR/Cas-Based Cell Therapy for Type 1 Diabetes: How Not to Engineer a "Trojan Horse".International journal of molecular sciences · 2023Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Cell therapies that rely on engineered immune cells can be enhanced by achieving uniform and controlled transgene expression in order to maximize T-cell function and achieve predictable patient responses. Although they are effective, current genetic engineering strategies that use γ-retroviral, lentiviral, and transposon-based vectors to integrate transgenes, unavoidably produce variegated transgene expression in addition to posing a risk of insertional mutagenesis. In the setting of chimeric antigen receptor (CAR) therapy, inconsistent and random CAR expression may result in tonic signaling, T-cell exhaustion, and variable T-cell persistence. Here, we report and validate an algorithm for the identification of extragenic genomic safe harbors (GSH) that can be efficiently targeted for DNA integration and can support sustained and predictable CAR expression in human peripheral blood T cells. The algorithm is based on 7 criteria established to minimize genotoxicity by directing transgene integration away from functionally important genomic elements, maximize efficient CRISPR/Cas9-mediated targeting, and avert transgene silencing over time. T cells engineered to express a CD19 CAR at GSH6, which meets all 7 criteria, are curative at low cell dose in a mouse model of acute lymphoblastic leukemia, matching the potency of CAR T cells engineered at the TRAC locus and effectively resisting tumor rechallenge 100 days after their infusion. The identification of functional extragenic GSHs thus expands the human genome available for therapeutic precision engineering.
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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.