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    Glycine-terminated dendritic amphiphiles for nonviral gene delivery (2012)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Malhotra, Shashwat
    Bauer, Hannah
    Tschiche, Ariane
    Staedtler, Anna Maria
    Mohr, Andreas
    Calderón, Marcelo
    Parmar, Virinder S
    Hoeke, Lena
    Sharbati, Soroush
    Einspanier, Ralf
    Haag, Rainer
    Forschungsprojekt
    Biokompatible siRNA-Nanotransporter für das zielgerichtete mRNAknock-down in vivo - Teilvorhaben: Synthese, Charakterisierung und biologische Evaluierung dendritischer Polyamine, bzw. Amphiphile 1., 2. u. 3. Generation
    Quelle
    Biomacromolecules; 13(10) — S. 3087–3098
    ISSN: 1525-7797
    Sprache
    Englisch
    Verweise
    DOI: 10.1021/bm300892v
    Pubmed: 22877231
    Kontakt
    Institut für Veterinär-Biochemie

    Oertzenweg 19 b
    14163 Berlin
    Tel.+49 30 838 62225 Fax.+49 30 838-62584
    email:biochemie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Development of nonviral vectors for the successful application of gene therapy through siRNA/DNA transfection of cells is still a great challenge in current research. (1, 2) In the present study, we have developed multivalent polyglycerol dendron based amphiphiles with well-defined molecular structures that express controlled glycine arrays on their surfaces. The structure-activity relationships with respect to the siRNA complexation, toxicity, and transfection profiles were studied with synthesized amphiphilic polycations. Our findings revealed that a second-generation amphiphilic dendrimer (G2-octaamine, 4) that has eight amine groups on its surface and a hydrophobic C-18 alkyl chain at the core of the dendron, acts as an efficient vector to deliver siRNA and achieve potent gene silencing by investigating the knockdown of luciferase and GAPDH gene activity in HeLa cells. Interestingly, the amphiphilic vector is nontoxic even at higher ratio of N/P 100. To the best of our knowledge this is the first example of successful in vitro siRNA transfection using dendritic amphiphiles. We believe that this supramolecular complex may serve as a new promising alternative for nonviral siRNA delivery systems and will be investigated for in vivo siRNA delivery in the future.