Splicesome mediated trans-RNA splicing (SMART)
A novel approach for gene therapy. described as SMART, was reported in January 2002. In this approach, an exogenous DNA, coding for trans-splice mRNA (mRNA. which will undergo trans-splicing with native endogenous mRNA) is introduced as a part of gene therapy. The exogenous DNA is designed to contain the following sequences in 5' to 3' order:

(i) a binding domain (at 5' end) that hybridizes to the intron present towards 5' to the defective exon, to be corrected. (ii) a spacer and (iii) at its 3' end, a 3' splice branchpoint and acceptor, which lies 5' to the defective exon. The mRNA transcribed from this introduced exogenous DNA and the defective endogenous mRNA are spliced and rejoined in such a manner, that the native mRNA will be corrected for the mutation.