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@ARTICLE{Hou:300351,
      author       = {Z. Hou and Q. Yi and M. Wu and L. Wu and F. Li$^*$ and T.
                      Wang and P. Bian},
      title        = {{A}ssessment and {M}itigation of {CRISPR}-{C}as9-{I}nduced
                      {N}ontargeted {T}ranslocations.},
      journal      = {Advanced science},
      volume       = {12},
      number       = {21},
      issn         = {2198-3844},
      address      = {Weinheim},
      publisher    = {Wiley-VCH},
      reportid     = {DKFZ-2025-00785},
      pages        = {e2414415},
      year         = {2025},
      note         = {2025 Jun;12(21):e2414415},
      abstract     = {The performance of CRISPR-mediated genome editing near
                      inverted repeats (IRs) potentially results in chromosomal
                      translocations and other catastrophic rearrangements.
                      However, the extent of this risk may be significantly
                      underestimated because current reporter systems focus solely
                      on site-specific translocations. Here, trans-acting reporter
                      systems in Escherichia coli are developed to detect
                      nontargeted translocations. Markedly increased frequency of
                      translocations following CRISPR-Cas9 activation is observed,
                      with the magnitude determined primarily by the length of the
                      IRs and the proximity between Cas9 target sites and IRs.
                      These translocations arise through a combination of
                      intramolecular single-strand annealing and alternative
                      end-joining mechanisms. Furthermore, it is discovered that
                      introducing segments homologous to IR loci can substantially
                      mitigate nontargeted translocations without significantly
                      compromising CRISPR-Cas9-mediated editing. The study
                      provides valuable insights into the genetic risks associated
                      with CRISPR technologies and suggests a viable strategy for
                      developing genetically safer CRISPR systems.},
      keywords     = {CRISPR‐mediated genome editing (Other) / DNA
                      single‐strand annealing (Other) / alternative
                      end‐joining (Other) / chromosomal rearrangement (Other) /
                      nontargeted translocation (Other)},
      cin          = {ED01},
      ddc          = {624},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40213940},
      doi          = {10.1002/advs.202414415},
      url          = {https://inrepo02.dkfz.de/record/300351},
}