RNA Trans-Splicing Modulation via Antisense Molecule Interference

Int J Mol Sci. 2018 Mar 7;19(3):762. doi: 10.3390/ijms19030762.


In recent years, RNA trans-splicing has emerged as a suitable RNA editing tool for the specific replacement of mutated gene regions at the pre-mRNA level. Although the technology has been successfully applied for the restoration of protein function in various genetic diseases, a higher trans-splicing efficiency is still desired to facilitate its clinical application. Here, we describe a modified, easily applicable, fluorescence-based screening system for the generation and analysis of antisense molecules specifically capable of improving the RNA reprogramming efficiency of a selected KRT14-specific RNA trans-splicing molecule. Using this screening procedure, we identified several antisense RNAs and short rationally designed oligonucleotides, which are able to increase the trans-splicing efficiency. Thus, we assume that besides the RNA trans-splicing molecule, short antisense molecules can act as splicing modulators, thereby increasing the trans-splicing efficiency to a level that may be sufficient to overcome the effects of certain genetic predispositions, particularly those associated with dominantly inherited diseases.

Keywords: KRT14; RNA therapy; RNA trans-splicing; antisense molecules; epidermolysis bullosa; fluorescence-based screening system.

MeSH terms

  • Cell Line
  • Gene Editing
  • Gene Expression Regulation*
  • Genes, Reporter
  • Humans
  • Oligonucleotides, Antisense*
  • RNA Interference*
  • RNA Splice Sites
  • RNA Splicing*
  • Trans-Splicing*


  • Oligonucleotides, Antisense
  • RNA Splice Sites