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Int. J. Mol. Sci. 2015, 16(1), 1179-1191; doi:10.3390/ijms16011179

Trans-Splicing Improvement by the Combined Application of Antisense Strategies

Department of Dermatology and EB House Austria, Paracelsus Medical University, Salzburg 5020, Austria
These authors contributed equally to this work.
Authors with joint senior authorship.
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Authors to whom correspondence should be addressed.
Academic Editor: Akila Mayeda
Received: 21 November 2014 / Accepted: 25 December 2014 / Published: 6 January 2015
(This article belongs to the Special Issue Pre-mRNA Splicing)
View Full-Text   |   Download PDF [1540 KB, uploaded 6 January 2015]   |  

Abstract

Spliceosome-mediated RNA trans-splicing has become an emergent tool for the repair of mutated pre-mRNAs in the treatment of genetic diseases. RNA trans-splicing molecules (RTMs) are designed to induce a specific trans-splicing reaction via a binding domain for a respective target pre-mRNA region. A previously established reporter-based screening system allows us to analyze the impact of various factors on the RTM trans-splicing efficiency in vitro. Using this system, we are further able to investigate the potential of antisense RNAs (AS RNAs), presuming to improve the trans-splicing efficiency of a selected RTM, specific for intron 102 of COL7A1. Mutations in the COL7A1 gene underlie the dystrophic subtype of the skin blistering disease epidermolysis bullosa (DEB). We have shown that co-transfections of the RTM and a selected AS RNA, interfering with competitive splicing elements on a COL7A1-minigene (COL7A1-MG), lead to a significant increase of the RNA trans-splicing efficiency. Thereby, accurate trans-splicing between the RTM and the COL7A1-MG is represented by the restoration of full-length green fluorescent protein GFP on mRNA and protein level. This mechanism can be crucial for the improvement of an RTM-mediated correction, especially in cases where a high trans-splicing efficiency is required. View Full-Text
Keywords: RNA trans-splicing; antisense oligonucleotides; RNA repair; genetic diseases RNA trans-splicing; antisense oligonucleotides; RNA repair; genetic diseases
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Koller, U.; Hainzl, S.; Kocher, T.; Hüttner, C.; Klausegger, A.; Gruber, C.; Mayr, E.; Wally, V.; Bauer, J.W.; Murauer, E.M. Trans-Splicing Improvement by the Combined Application of Antisense Strategies. Int. J. Mol. Sci. 2015, 16, 1179-1191.

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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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