% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Bozza:157016,
      author       = {M. Bozza$^*$ and E. W. Green$^*$ and E. Espinet$^*$ and A.
                      De Roia$^*$ and C. Klein$^*$ and V. Vogel$^*$ and R.
                      Offringa$^*$ and J. A. Williams and M. Sprick$^*$ and R.
                      Harbottle$^*$},
      title        = {{N}ovel {N}on-integrating {DNA} {N}ano-{S}/{MAR} {V}ectors
                      {R}estore {G}ene {F}unction in {I}sogenic
                      {P}atient-{D}erived {P}ancreatic {T}umor {M}odels.},
      journal      = {Molecular therapy Methods $\&$ clinical development},
      volume       = {17},
      issn         = {2329-0501},
      address      = {New York, NY},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2020-01313},
      pages        = {957 - 968},
      year         = {2020},
      note         = {#EA:F160#LA:F160#},
      abstract     = {We describe herein non-integrating minimally sized
                      nano-S/MAR DNA vectors, which can be used to genetically
                      modify dividing cells in place of integrating vectors. They
                      represent a unique genetic tool, which avoids
                      vector-mediated damage. Previous work has shown that DNA
                      vectors comprising a mammalian S/MAR element can provide
                      persistent mitotic stability over hundreds of cell
                      divisions, resisting epigenetic silencing and thereby
                      allowing sustained transgene expression. The composition of
                      the original S/MAR vectors does present some inherent
                      limitations that can provoke cellular toxicity. Herein, we
                      present a new system, the nano-S/MAR, which drives higher
                      transgene expression and has improved efficiency of
                      establishment, due to the minimal impact on cellular
                      processes and perturbation of the endogenous transcriptome.
                      We show that these features enable the hitherto challenging
                      genetic modification of patient-derived cells to stably
                      restore the tumor suppressor gene SMAD4 to a patient-derived
                      SMAD4 knockout pancreatic cancer line. Nano-S/MAR
                      modification does not alter the molecular or phenotypic
                      integrity of the patient-derived cells in cell culture and
                      xenograft mouse models. In conclusion, we show that
                      these DNA vectors can be used to persistently modify a
                      range of cells, providing sustained transgene expression
                      while avoiding the risks of insertional mutagenesis and
                      other vector-mediated toxicity.},
      cin          = {F160 / D170 / A010 / V960 / D200},
      ddc          = {610},
      cid          = {I:(DE-He78)F160-20160331 / I:(DE-He78)D170-20160331 /
                      I:(DE-He78)A010-20160331 / I:(DE-He78)V960-20160331 /
                      I:(DE-He78)D200-20160331},
      pnm          = {316 - Infections and cancer (POF3-316)},
      pid          = {G:(DE-HGF)POF3-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32420409},
      pmc          = {pmc:PMC7218229},
      doi          = {10.1016/j.omtm.2020.04.017},
      url          = {https://inrepo02.dkfz.de/record/157016},
}