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.
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Acknowledgements
This study was supported by the Netherlands Foundation for Scientific Research (NWO, project 901-01-096), the Netherlands Heart Foundation (project M93 001) and the Chemical Sciences/Foundation of Technical Sciences (CW/STW, project 349-4779).
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van Rossenberg, S., van Keulen, A., Drijfhout, JW. et al. Stable polyplexes based on arginine-containing oligopeptides for in vivo gene delivery. Gene Ther 11, 457–464 (2004). https://doi.org/10.1038/sj.gt.3302183
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DOI: https://doi.org/10.1038/sj.gt.3302183