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@ARTICLE{Siewert:859326,
      author       = {Siewert, C. and Haas, H. and Nawroth, T. and Ziller, A. and
                      Nogueira, S. S. and Schroer, M. A. and Blanchet, C. E. and
                      Svergun, D. I. and Radulescu, Aurel and Bates, F. and
                      Huesemann, Y. and Radsak, M. P. and Sahin, U. and Langguth,
                      P.},
      title        = {{I}nvestigation of charge ratio variation in m{RNA} –
                      {DEAE}-dextran polyplex delivery systems},
      journal      = {Biomaterials},
      volume       = {192},
      issn         = {0142-9612},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {FZJ-2019-00195},
      pages        = {612 - 620},
      year         = {2019},
      abstract     = {mRNA pharmaceuticals represent a new class of therapeutics,
                      with applications, in cancer vaccination, tumour therapy and
                      protein substitution. Formulations are required to deliver
                      messenger RNA (mRNA) to the target sites where induction of
                      genetic transfection following receptor mediated cell uptake
                      $\&$ translation is required.In the current study, the
                      cationic polysaccharide diethylaminoethylen (DEAE) –
                      Dextran was selected as a model system carrier for the
                      investigation of polyplex nanoparticle formation together
                      with mRNA as a function of the molar ratio of the
                      components. The structure of the mRNA/Dextran colloids was
                      investigated as a function of the polymer-to-mRNA ratio and
                      correlated with the biological activity determined by
                      cellular transfection with luciferase coding mRNA. Dynamic
                      light scattering (DLS), small angle x-ray scattering (SAXS),
                      and small angle neutron scattering (SANS) with deuterium
                      contrast variation were used to achieve structural insight
                      into the systems. Similarly to previously investigated lipid
                      based systems, colloidally stable particles with confined
                      size were obtained with either excess of positive or
                      negative charge. Highest activity was obtained with positive
                      charge excess. From the scattering experiments information
                      on the internal organization inside the polymer/mRNA systems
                      was derived. Indication for the presence of structural
                      elements in the length scale of ten to 20 nm were found in
                      the excess of dextran, which could be due to either excess
                      or particulate polymer. Information on the molecular
                      organization of the mRNA nanoparticle products may provide a
                      valuable basis for defining critical quality attributes of
                      drug products for pharmaceutical application.},
      cin          = {JCNS-FRM-II / Neutronenstreuung ; JCNS-1},
      ddc          = {570},
      cid          = {I:(DE-Juel1)JCNS-FRM-II-20110218 /
                      I:(DE-Juel1)JCNS-1-20110106},
      pnm          = {6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623)
                      / 6G15 - FRM II / MLZ (POF3-6G15)},
      pid          = {G:(DE-HGF)POF3-6G4 / G:(DE-HGF)POF3-6G15},
      experiment   = {EXP:(DE-MLZ)KWS2-20140101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30502967},
      UT           = {WOS:000456902000050},
      doi          = {10.1016/j.biomaterials.2018.10.020},
      url          = {https://juser.fz-juelich.de/record/859326},
}