Gene therapy relies on nucleic acid carriers. The diversity of viruses allows to fulfil most requirements for gene delivery in clinical situations. However, a parallel evolution of viruses and their hosts has made foreign protein particles, as well as infected cells, effective targets for the immune system. Synthetic supramolecular vectors can be designed without polypeptides and can even be coated with an inert layer, thus escaping most of the immune surveil-lance. Unfortunately, at best a few out of a billion copies of the gene reach the target cell nucleus. Unfavourable biodistribution as well as ineffective intracellular trafficking are responsible for this poor figure.