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Endocytosis in gene therapy with non-viral vectors

Endozytose in der Gentherapie mit nichtviralen Vektoren

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Summary

Gene therapy or the delivery of genetic material can be carried out not only with viral vectors, but with non-viral vectors too. Although the use of non-viral carriers is safer, this approach has generally been poorer in terms of transfection efficiency. In order to improve the transfection rates, it is important to exactly know the path that the nanoparticles go through. In this way, we can understand the reason why some of these vectors fail or are successful in their duties. This review aims to summarize the different stages and barriers that nanocarriers have to overcome during endocytosis so as to reach the cytoplasm, in the case of RNA, or the nucleus, in the case of DNA. In addition, different strategies that could be employed to improve the success of the carriers in each stage are suggested.

Zusammenfassung

Gentherapie oder die Einschleusung von genetischem Material kann nicht nur mit viralen Vektoren durchgeführt werden, sondern auch mit nichtviralen Vektoren. Obwohl die Verwendung von nichtviralen Trägern sicherer ist, hat sich diese Alternative im Allgemeinen als ungünstiger in Bezug auf die Transfektionseffizienz erwiesen. Um die Transfektionsraten zu verbessern, ist es wichtig, den Weg, den die Nanopartikel durchlaufen, ganz genau zu kennen. Auf diese Weise können wir verstehen, warum einige dieser Vektoren scheitern oder bei ihren Aufgaben erfolgreich sind. Diese Übersichtsarbeit zielt darauf ab, die verschiedenen Stufen und Barrieren zusammenfassen, welche die Nanopartikel während der Endozytose durchlaufen oder überwinden müssen, um – im Fall von RNA – das Zytoplasma zu erreichen oder – im Fall von DNA – den Zellkern. Zusätzlich werden verschiedene Strategien zur Verbesserung der Wirkung von Vektoren in den jeweiligen Stadien vorgeschlagen.

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Acknowledgements

I want to acknowledge Prof. Renate Fuchs for her priceless help both during my first steps in the study of the endocytosis as well as for the impulse given to my PhD thesis and my further development as a better scientist.

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  1. Institut de Biologie Moléculaire et Cellulaire, Laboratoire d’Immunopathologie et Chimie Thérapeutique, CNRS, 67000, Strasbourg, France

    Aritz Perez Ruiz de Garibay

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Perez Ruiz de Garibay, A. Endocytosis in gene therapy with non-viral vectors. Wien Med Wochenschr 166, 227–235 (2016). https://doi.org/10.1007/s10354-016-0450-5

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