Fachbereich Veterinärmedizin



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

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Malhotra, Shashwat
    Bauer, Hannah
    Tschiche, Ariane
    Staedtler, Anna Maria
    Mohr, Andreas
    Calderón, Marcelo
    Parmar, Virinder S
    Hoeke, Lena
    Sharbati, Soroush
    Einspanier, Ralf
    Haag, Rainer
    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
    Biomacromolecules; 13(10) — S. 3087–3098
    ISSN: 1525-7797
    DOI: 10.1021/bm300892v
    Pubmed: 22877231
    Institut für Veterinär-Biochemie

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    14163 Berlin
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    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.