Gene therapy approaches that target either viral or defective cellular genes at the level of mRNA have focused on disruption of gene function, and include antisense technology to inhibit translation or use of an engineered ribozyme to cleave the message. In this issue, Puttaraju and colleagues have come up with a way of hijacking the cellular splicing machinery to actually repair genetic defects, and even reprogram gene expression, at the level of the message (pp. 223 and 246). Although not yet ready to be applied therapeutically, this work raises the tantalizing possibility that trans-splicing could one day be used as a platform to "rewrite" transcribed messages encoding disease-related genes.