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

Gene Therapy volume 11, pages 457–464 (2004)Cite this article

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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Author notes

  1. SMW van Rossenberg and ACI van Keulen: The first two authors contributed equally

Authors and Affiliations

  1. Division of Biopharmaceutics, Gorlaeus Laboratories, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands

    SMW van Rossenberg, ACI van Keulen, ThJC van Berkel & EAL Biessen

  2. Department of Immunohaematology, LUMC, Leiden, The Netherlands

    J-W Drijfhout

  3. Crucell NV, Archimedesweg, Leiden, The Netherlands

    S Vasto

  4. Laboratory for Electron Microscopy Leiden, LUMC, Leiden, The Netherlands

    HK Koerten, F Spies & JM van 't Noordende

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  1. SMW van Rossenberg
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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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