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@ARTICLE{Fazeli:307439,
      author       = {A. Fazeli and E. Ullrich$^*$ and T. Cathomen$^*$ and T.
                      Bexte$^*$},
      title        = {{E}ngineering with care: safety assessment platforms for
                      {CRISPR}-modified natural killer cells.},
      journal      = {Frontiers in immunology},
      volume       = {16},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2025-03038},
      pages        = {1711414},
      year         = {2025},
      abstract     = {CRISPR-based gene editing has become a transformative tool
                      to enhance immune cell therapies. In particular, engineering
                      natural killer (NK) cells with CRISPR/Cas systems has gained
                      traction due to their ability to mediate strong anti-tumor
                      responses in an MHC-unrestricted, non-alloreactive manner.
                      Early trials show the feasibility and safety of allogeneic
                      NK cells, paving the way as scalable 'off-the-shelf'
                      products. CRISPR/Cas9 edits genomes by inducing DNA
                      double-strand breaks (DSBs), mainly repaired through
                      non-homologous end joining (NHEJ) or homology-directed
                      repair (HDR). While effective, CRISPR carries risks of
                      off-target (OT) activity that may disrupt essential genes,
                      cause chromosomal rearrangements, or trigger oncogenic
                      changes - posing threats to product integrity and patient
                      safety. These concerns intensify with multiplex editing,
                      where multiple loci are modified to improve function,
                      persistence, and immune evasion. Since unmodified NK cells
                      are typically short-lived, many clinical-stage products are
                      engineered to express IL-15 or related constructs, extending
                      their half-life and amplifying risks associated with
                      unintended changes. This underscores the urgent need for
                      robust safety assessments. In this review, we summarize the
                      current landscape of safety assessment platforms for
                      evaluating gene edited NK cells. We highlight predictive in
                      silico tools, biochemical in vitro assays, and emerging
                      cell-based detection systems to identify and quantify
                      CRISPR-induced OT events. Particular attention is given to
                      their suitability, limitations, and practical use in primary
                      NK cells and multiplex editing strategies. Our aim is to
                      support the design of safe, effective editing workflows for
                      NK cell therapies - ensuring rigor as the field advances
                      rapidly toward clinical application.},
      subtyp        = {Review Article},
      keywords     = {Killer Cells, Natural: immunology / Killer Cells, Natural:
                      metabolism / Killer Cells, Natural: transplantation / Humans
                      / Gene Editing: methods / CRISPR-Cas Systems / Animals /
                      Immunotherapy, Adoptive: methods / Immunotherapy, Adoptive:
                      adverse effects / CRISPR (Other) / NK cells (Other) /
                      allogenic (Other) / cell therapy (Other) / gene-editing
                      (Other) / off-target (Other) / safety assessment (Other)},
      cin          = {FM01 / FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331 / I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41425600},
      pmc          = {pmc:PMC12714958},
      doi          = {10.3389/fimmu.2025.1711414},
      url          = {https://inrepo02.dkfz.de/record/307439},
}