Within this study we report for the first time, that the combined application of RNA trans-splicing molecules (RTM) and antisense oligonucleotides (AS RNAs) can significantly increase the trans-splicing efficiency of a selected RTM specific for the EB-associated gene COL7A1. The important innovative aspect of this study is the establishment of an unbiased RTM and AS RNA screening method that can be used not only for the improvement of COL7A1 repair, but also for other genes affected in EB as well as other genetic diseases. Here, COL7A1 is linked to epidermolysis bullosa.