Successful gene therapy relies upon being able to target the injury site, and to control the duration and levels of gene expression. Modifying the transgene DNA to exclude nonmethylated CpG motifs, typical of bacterial DNA, decreases the immune response and may increase transgene expression [75, 76] . High-effi ciency tissue-specifi c promoters may improve the effi ciency and specifi city of transgene expression. Lung-specifi c promoters include surfactant promoters [77] such as the surfactant protein C promoter [78] , a ciliated cell-specifi c promoter FOXJ1 [79] , the cytokeratin 18 promoter [80] , and the Clara cell 10-kDa protein [78] . Promoters can also be used to target a specifi c phase of illness, switching on when required to produce an eff ect at the optimal time point. A related approach is the development of promoters that allow for transfected genes to be turned on and off . Currently, the tetracycline-dependent gene expression vector [81] is the most widely used regulated system as it has a good safety profi le. Tetracycline is rapidly metabolized and cleared from the body, making it an ideal drug to control gene expression. However, the potential for an activator such as tetracycline to modulate the lung injury should be borne in mind. New-generation transactivators, with no basal activity and increased sensitivity, have now been developed [82] . In an ARDS context, conditional regulation of gene expression by the combined use of a lung-specifi c promoter and the tetracycline-dependent gene expression system may be a useful approach [83] . Capsid protein modifi cation to reduce immunogenicity [71] Capsid protein modifi cation to enhance tissue specifi city [70] Envelope protein pseudotyping