Minding the Cs and Gs

Successful gene therapy requires the introduction of foreign DNA into host cells. Until recently, most investigators working in this field did not realize that the DNA sequences themselves contained immune stimulatory sequences, called CpG motifs, that activate immune responses as an unintended consequence of gene delivery. DNA containing CpG motifs activates both the innate and the acquired arms of immune responses (Fig. 1). CpG-induced innate immunity is exemplified by the rapid activation of NK cells, macrophages, and dendritic cells, with the concomitant production of proinflammatory cytokines.