ArticleNature biotechnology2025
SEED-Selection enables high-efficiency enrichment of primary T cells edited at multiple loci.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Synergistic immune interactions between T cells and natural killer cells in allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: current status and future directions.Annals of medicine · 2026Review
- Engineering CAR T Cells for Hepatocellular Carcinoma Recurrence after Liver Transplantation.bioRxiv : the preprint server for biology · 2026Article
- Dual CD8 and TCR editing in regulatory T cells mediates HLA-A2-restricted tissue-specific homing.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Ultra-large targeted DNA integrations in primary human cells.bioRxiv : the preprint server for biology · 2026Article
- Engineering Immune Cell to Counteract Aging and Aging-Associated Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Reversible control of T cell exhaustion by NR4A transcription factors revealed through targeted protein degradation.bioRxiv : the preprint server for biology · 2026Article
- Research on the Mechanism of "Cold Tumor" Formation and Immunotherapy for Its Transformation into "Hot Tumor".Oncology research · 2026Review
- Imaging CRISPR-edited CAR-T cell therapies with optical and positron emission tomography reporters.Theranostics · 2026Article
- Integrating synthetic biology to understand and engineer the heart, lung, blood, and sleep systems.Cell systems · 2025Review
- Search-and-remove genome editing allows selection of cells by DNA sequence.Nature communications · 2025Article
- A unified genetic perturbation language for human cellular programming.bioRxiv : the preprint server for biology · 2025Article
- Site-specific genome engineering of primary human natural killer cells for programmable anti-tumor function.bioRxiv : the preprint server for biology · 2025Article
- Base-editing a single missense mutation in A20 enhances CAR-T cell efficacy.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
18 authors.
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Abstract
Engineering T cell specificity and function at multiple loci can generate more effective cellular therapies, but current manufacturing methods produce heterogenous mixtures of partially engineered cells. Here we develop a one-step process to enrich unlabeled cells containing knock-ins at multiple target loci using a family of repair templates named synthetic exon expression disruptors (SEEDs). SEEDs associate transgene integration with the disruption of a paired target endogenous surface protein while preserving target expression in nonmodified and partially edited cells to enable their removal (SEED-Selection). We design SEEDs to modify three critical loci encoding T cell specificity, coreceptor expression and major histocompatibility complex expression. The results demonstrate up to 98% purity after selection for individual modifications and up to 90% purity for six simultaneous edits (three knock-ins and three knockouts). This method is compatible with existing clinical manufacturing workflows and can be readily adapted to other loci to facilitate production of complex gene-edited cell therapies.
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