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SONYA VASTO

Stable polyplexes based on arginine-containing oligopeptides for in vivo gene delivery.

  • Autori: VAN ROSSENBERG, S.; VAN KEULEN, A.; Drijfhout, J.; Vasto, S.; Koerten, H.; Spies, F.; VAN 'T NOORDENDE, J.; VAN BERKEL, T.; Biessen, E.
  • Anno di pubblicazione: 2004
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • OA Link: http://hdl.handle.net/10447/3684

Abstract

In this study, we investigated to what extent the stability and transduction capacity of polyplexed DNA can be improved by optimizing the condensing peptide sequence. We have synthesized a small library of cationic peptides, at which the lysine/arginine ratio and the cation charge were varied. All peptides were able to compact DNA, at which polyplexes of short lysine-rich sequences were considerably larger than those of elongated or arginine-rich peptides (GM102 and GM202). In addition, the arginine-rich peptides GM102 and GM202 rendered the polyplexes resistant to plasma incubation or DNase I-mediated digestion. While all peptides were found to improve the transfection efficiency in HepG2 cells, only the GM102- and GM202-derived polyplexes could be specifically targeted to HepG2 cells by incorporation of a ligand-derivatized YKAK8WK peptide. We propose that GM102 and GM202 combine the advantage of small condensing peptides to give small-sized polyplexes with the superior stability of condensing polymers, which makes GM102 and GM202 excellent candidates for future in vivo gene therapy studies.