Spliceosome-mediated RNA trans-splicing (SMaRT) is a tool that facilitates the recombination of two distinct pre-mRNA molecules. Its application for gene therapeutic purposes has been hindered by laborious procedures to identify gene-specific molecules. We have established a screening method for the identification of highly functional RNA trans-splicing molecules based on fluorescence reporters, facilitating the generation of most potent therapeutic molecules for the correction of any gene of interest.