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Utilization of synthetic peptides containing nuclear localization signals for nonviral gene transfer systems

Gene Therapy volume 9, pages 157–167 (2002)Cite this article

Abstract

The ability of nonviral gene delivery systems to overcome extracellular and intracellular barriers is a critical issue for future clinical applications. In recent years, several efforts were focused on the elucidation of the gene transfer mechanisms and on the development of multicomponent systems in order to improve both targeted gene delivery and transfection efficiency. The transport of the therapeutic DNA from the cytoplasm into the nucleus is an inefficient process and is considered as the major limiting step in nondividing cells. One of the strategies to improve nuclear uptake of DNA is taking advantage of the cellular nuclear import machinery. Synthetic peptides containing a nuclear localization signal (NLS) are bound to the DNA so that the resulting DNA–NLS complex can be recognized as a nuclear import substrate by specific intracellular receptor proteins. In this review, we critically summarize recent studies applying this approach with a particular focus on NLS-sequence specificity. Implications of the observed results are also discussed in regards to future developments of this technology.

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Acknowledgements

We wish to thank Peter Scherrer for helpful discussions and suggestions during the preparation of the manuscript. We are also grateful to Michael Böttger and Katja Heuer for critical reading.

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  1. Max-Delbrück Center for Molecular Medicine, Drug Targeting, Berlin, Germany

    R Cartier & R Reszka

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Cartier, R., Reszka, R. Utilization of synthetic peptides containing nuclear localization signals for nonviral gene transfer systems. Gene Ther 9, 157–167 (2002). https://doi.org/10.1038/sj.gt.3301635

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