Targeted in vivo delivery of nucleic acids by lipid-based carriers

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This thesis focuses on the development of targeted liposomal carriers for the delivery of antisense ODN and DNA in vivo to various cell types in the liver. The power of the antisense approach as well as of DNA transfection has been thoroughly characterized in numerous in vitro studies. However, these techniques need substantial research efforts to establish continuing progress in delivery strategies: the safe and versatile delivery of genes and ODNs has developed into a key issue in the progress of gene therapy. This study describes the development of liver cell targeted ODN and gene carriers. For the construction of a serum-stable carrier we followed two concepts: 1. the neutral coating of preformed cationic lipid/ODN lipoplexes (coated cationic lipoplexes or CCLs) and 2. the encapsulation of ODN or DNA in a liposome-like structure including cationic lipids (stabilized antisense (plasmid) lipid particles or SALPs/SPLPs). ....

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