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- Title
Stable polyplexes based on arginine-containing oligopeptides for in vivo gene delivery.
- Authors
van Rossenberg, S. M. W.; van Keulen, A. C. I.; Drijfhout, J. -W.; Vasto, S.; Koerten, H. K.; Spies, F.; van't Noordende, J. M.; van Berkel, Th. J. C.; Biessen, E. A. L.
- 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.Gene Therapy (2004) 11, 457-464. doi:10.1038/sj.gt.3302183
- Subjects
PEPTIDES; GENETIC transduction; LYSINE; ARGININE; POLYMERIZATION; GENE therapy
- Publication
Gene Therapy, 2004, Vol 11, Issue 5, p457
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302183