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@ARTICLE{Hartmann:168225,
      author       = {O. Hartmann and M. Reissland and C. R. Maier$^*$ and T.
                      Fischer and C. Prieto-Garcia and A. Baluapuri and J. Schwarz
                      and W. Schmitz and M. Garrido-Rodriguez and N. Pahor and C.
                      C. Davies and F. Bassermann and A. Orian and E. Wolf and A.
                      Schulze$^*$ and M. A. Calzado and M. T. Rosenfeldt and M. E.
                      Diefenbacher},
      title        = {{I}mplementation of {CRISPR}/{C}as9 {G}enome {E}diting to
                      {G}enerate {M}urine {L}ung {C}ancer {M}odels {T}hat {D}epict
                      the {M}utational {L}andscape of {H}uman {D}isease.},
      journal      = {Frontiers in cell and developmental biology},
      volume       = {9},
      issn         = {2296-634X},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2021-00756},
      pages        = {641618},
      year         = {2021},
      abstract     = {Lung cancer is the most common cancer worldwide and the
                      leading cause of cancer-related deaths in both men and
                      women. Despite the development of novel therapeutic
                      interventions, the 5-year survival rate for non-small cell
                      lung cancer (NSCLC) patients remains low, demonstrating the
                      necessity for novel treatments. One strategy to improve
                      translational research is the development of surrogate
                      models reflecting somatic mutations identified in lung
                      cancer patients as these impact treatment responses. With
                      the advent of CRISPR-mediated genome editing, gene deletion
                      as well as site-directed integration of point mutations
                      enabled us to model human malignancies in more detail than
                      ever before. Here, we report that by using
                      CRISPR/Cas9-mediated targeting of Trp53 and KRas, we
                      recapitulated the classic murine NSCLC model Trp53 fl/fl
                      :lsl-KRas G12D/wt . Developing tumors were indistinguishable
                      from Trp53 fl/fl :lsl-KRas G12D/ wt -derived tumors with
                      regard to morphology, marker expression, and transcriptional
                      profiles. We demonstrate the applicability of CRISPR for
                      tumor modeling in vivo and ameliorating the need to use
                      conventional genetically engineered mouse models.
                      Furthermore, tumor onset was not only achieved in
                      constitutive Cas9 expression but also in wild-type animals
                      via infection of lung epithelial cells with two discrete
                      AAVs encoding different parts of the CRISPR machinery. While
                      conventional mouse models require extensive husbandry to
                      integrate new genetic features allowing for gene targeting,
                      basic molecular methods suffice to inflict the desired
                      genetic alterations in vivo. Utilizing the CRISPR toolbox,
                      in vivo cancer research and modeling is rapidly evolving and
                      enables researchers to swiftly develop new, clinically
                      relevant surrogate models for translational research.},
      keywords     = {CRISPR-Cas9 (Other) / JUN (Other) / KRAS (Other) / MYC
                      (Other) / TP53 (Other) / lung cancer (Other) / mouse model
                      (Other) / non-small cell lung cancer (Other)},
      cin          = {A410},
      ddc          = {570},
      cid          = {I:(DE-He78)A410-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33738287},
      pmc          = {pmc:PMC7961101},
      doi          = {10.3389/fcell.2021.641618},
      url          = {https://inrepo02.dkfz.de/record/168225},
}