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We are very grateful to Drs. Shunji Tomatsu and Adriana Montaño for a long time collaboration in research in this and other areas. This work was supported in part by Pontificia Universidad Javeriana (Projects ID 3763 and 4423). Rocío Cuaspa received a young researcher fellowship from the Administrative Department of Science, Technology and Innovation from Colombia (COLCIENCIAS). The authors thank María Lucía Gutiérrez and Dr. Bernd Stab for assistance with editing of the manuscript.

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**4** 

*Germany*

**Investigation of Transfection Barriers Involved in Non-Viral Nanoparticulate** 

**Gene Delivery in Different Cell Lines** 

*Department of Pharmaceutical Technology and Biopharmacy, Freiburg* 

In order to improve the delivery efficiency of genetic material into cells both *in vitro* and *in vivo*, the development of effective non viral vectors for optimized gene transfer into target cells has become an important objective. Non-viral vector systems in particular, such as cationic lipids and polymers, have been widely investigated as to their suitability as a delivery system [1-4]. In cell lines, non-viral gene transfer mediated by cationic lipid/DNA aggregates has been accomplished efficiently showing no immunogenicity and low cytotoxicity [5]. Unfortunately, non-viral gene transfer into primary cells is still inefficient and results in low transgene expression *in vivo* [6]. In contrast to the transfection of most cell lines, which can be successfully performed using a variety of methods, the introduction of foreign DNA into primary cells requires careful selection of the gene transfer technique. Whereas viral strategies are involved in immunogenic risks, non-viral methods have proved to be inefficient for most primary cell types. This might be due to the fact that biological

Therefore, knowledge about the uptake mechanism and the subsequent intracellular processing of non-viral gene delivery systems is important for the development of efficient gene delivery systems. Moreover, in understanding the internalization of particles into cells,

Multiple processes are thought to be involved in the cellular internalization of particles [7], whereas clathrin-dependent uptake is the one which has been investigated the most. However, other internalization pathways such as the caveolae-dependent pathway, macropinocytosis, phagocytosis and the non-clathrin-non-caveolae dependent pathway are

The mode of internalization may affect the kinetics of intracellular processing as well as transfection efficiency. Depending on the uptake mechanism a variety of obstacles could be the reason for low transfection efficiency. Also depending on the mode of cellular uptake, internalization may lead to either lysosomal degradation and digestion, recycling back to the membrane, transcytotic transport across the epithelial barrier or delivery to other

Once having been released into the cytosol, additional barriers such as insufficient desaggregation of the complex, poor cytoplasmic transport, cytosolic digestion by means of

barriers have to be overcome in order to achieve successful gene delivery.

possible ways for gene delivery and further processing in the cells as well [8].

**1. Introduction** 

distinct pathways might be targeted.

compartments.

Stefanie Häfele and Regine Süss

for foreign peptide incorporation. *Journal of Virology*. Vol. 79, No. 6, (March 2005), pp. 3382-3390, ISSN 0022-538X.

