The use of natural viral or cellular promoters to express a therapeutic gene has met with only limited success, as a result of low levels of transcription or inactivation of the promoter following transfer to the target tissue. Refusing to be limited to the collection of natural muscle-specific promoters, Schwartz and colleagues decided to create synthetic promoters of their own (see pp. 224 and 241). By randomly mixing and matching four distinct promoter elements from known muscle-specific genes, they generated a library of synthetic shuffled promoters. Screening this library for tissue-specific expression, they succeeded in identifying a few promoters whose strength in differentiated muscle tissue greatly exceeded that of the natural promoters from which they were derived.