Gene therapy is one of the most rapidly growing areas in nanomedicine research. The delivery of foreign nucleic acids, e.g. siRNA, mRNA or DNA, into human cells offers huge opportunities for biomedical applications. Depending on the site of action of the nucleic acids, they may require escape from endosomes and delivery to the cytosol or nucleus. Gene delivery systems can be used to exert a therapeutic effect (i.e. introduction of a functional gene into cells suffering from a damaged gene), to modulate cellular functions (i.e. protein knockdown using siRNA), for monitoring purposes (i.e. using green fluorescent protein, GFP).

In general, gene delivery systems consist of a cationic polymer- or lipid-based substance to condensate negatively charged nucleic acids to nanoparticles. To reduce the cytotoxicity and moreover, to increase the blood circulation time, nanoparticles can further be shielded to reduce interactions with cell components or plasma proteins. This is often achieved by coupling of polyethylene glycol molecules to the surface of the nanoparticles (PEGylation). By coupling targeting ligands such as sugars or peptides to the surface of the nanoparticle, a targeted gene delivery can be achieved.

Our research is focused on new nanomaterials for an optimized loading and retention of nucleic acids for a systemic administration in vivo with high cytocompatibility (see Witzigmann et al, 2015).

TEM analysis of LNPs encapsulating plasmid DNA. Cellular uptake of DNA loaded LNPs followed by gene expression (GFP)