Since the first edition of this book in 1999 the field of gene therapy has been the arena both for major advances that justified the early hopes placed in the concept, and for ever-present impatience with the slowness of overall progress. On the positive side, gene therapy obtained its first brilliant success, though not where most efforts were invested and not with a synthetic vector (Cavazzana-Calvo et al., 2000). Yet the search for efficient molecules is still very active, in part because the negative consequences of using viral vectors somewhat shadow the brilliant picture (Hacein-Bey-Abina et al., 2003).