RNA Trans-Splicing Modulation via Antisense Molecule Interference

• Published in: International journal of molecular sciences Vol. 19; no. 3; p. 762
• Main Authors: Liemberger, Bernadette, Piñón Hofbauer, Josefina, Wally, Verena, Arzt, Claudia, Hainzl, Stefan, Kocher, Thomas, Murauer, Eva M, Bauer, Johann W, Reichelt, Julia, Koller, Ulrich
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.03.2018; MDPI
• Subjects: antisense molecules; Antisense RNA; Cell Line; Efficiency; epidermolysis bullosa; Eukaryotes; Fluorescence; fluorescence-based screening system; Gene Editing; Gene Expression Regulation; Genes, Reporter; Hereditary diseases; Humans; KRT14; mRNA; Oligonucleotides, Antisense; Proteins; RNA editing; RNA Interference; RNA Splice Sites; RNA Splicing; RNA therapy; RNA trans-splicing; RNA-mediated interference; Splicing; Trans-Splicing; RNA therapy; antisense molecules; epidermolysis bullosa; RNA trans-splicing; KRT14; fluorescence-based screening system
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19030762

In recent years, RNA -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 -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 -specific RNA -splicing molecule. Using this screening procedure, we identified several antisense RNAs and short rationally designed oligonucleotides, which are able to increase the -splicing efficiency. Thus, we assume that besides the RNA -splicing molecule, short antisense molecules can act as splicing modulators, thereby increasing the -splicing efficiency to a level that may be sufficient to overcome the effects of certain genetic predispositions, particularly those associated with dominantly inherited diseases.