RNA repair using spliceosome-mediated RNA trans-splicing

During the last decade, several elegant and disparate RNA-repair strategies have been developed for use as therapeutic interventions. One such approach, spliceosome-mediated RNA trans-splicing (SMaRT™), uses specialized constructs called pre-trans-splicing molecules (PTMs) that can bind to specific endogenous mutant nuclear RNAs and effect a trans-splicing event to create a composite repaired product. This and other RNA modifying technologies are a distinct departure from the traditional gene-therapy approach of ubiquitously expressing a full-length cDNA. RNA repair offers the potential advantages of maintaining endogenous regulation and the elimination of ectopic expression of the transgene. Here, we review the different RNA-repair strategies and discuss the advances that have been made for SMaRT™ technology to date and the potential advantages and limitations of SMaRT™ compared with traditional gene therapy.