Exon skipping therapy for dystrophic epidermolysis bullosa
Bremer, Jeroen
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2018
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Bremer, J. (2018). Exon skipping therapy for dystrophic epidermolysis bullosa. University of Groningen.
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Exon skipping therapy for
dystrophic epidermolysis bullosa
GUIDE
Cover image: Successful treatment of RDEB patient skin grafts (Chapter 2)
Background: Patient cells expressing type VII collagen upon exon skipping treatment.
Cover and layout design: Jeroen Bremer
Printed by: Gildeprint
©Copyright: Jeroen Bremer, 2018
No part of this thesis may be reproduced in any form or by any means, without prior
written permission of the author. The copyrights of the publications remain with the
publisher, unless stated otherwise.
The research described in this thesis was supported by the ERA-Net for Research
Programmes on Rare Diseases (E-RARE) grant: Splice-EB, Stichting Vlinderkind (Dutch
Butterfly Child Foundation), and Zeldzame Ziekten Fonds (Rare Disease Fund). Their
support is gratefully acknowledged in this thesis.
Exon skipping therapy for
dystrophic epidermolysis bullosa
PhD thesis
to obtain the degree of PhD at the University of Groningen
on the authority of the Rector Magnificus Prof. E. Sterken
and in accordance with the decision by the College of Deans. This thesis will be defended in public on Wednesday 25 April 2018 at 11:00 hours
by
Jeroen Bremer
born on 19 July 1988Dr. A.M.G. Pasmooij
Dr. P.C. van den Akker
Assessment committee
Prof. J.W. Bauer
Prof. R.M.W. Hofstra
Prof. R.A. Bank
Paranimfen
Joost Meijer
Antoni Gostyński
Contents
Ch. 1 Introduction... 9
Part one: Exon skipping as therapeutic approach Ch. 2 Antisense oligonucleotide-mediated exon skipping as therapeutic approach for recessive dystrophic epidermolysis bullosa... 31
Ch. 3 Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy... 51
Ch. 4 Murine type VII collagen distorts outcome in human skin graft mouse models for dystrophic epidermolysis bullosa... 77
Ch. 5 RNA-based therapies for genodermatoses... 89
Part two: Natural exon skipping Ch. 6 Natural exon skipping sets the stage for antisense oligonucleotide- mediated exon skipping as a therapeutic approach for dystrophic epidermolysis bullosa... 117
Ch. 7 Amelioration of junctional epidermolysis bullosa due to exon skipping... 139
Ch. 8 In-frame exon skipping in KRT5 due to novel intronic deletion causes epidermolysis bullosa simplex, generalized severe... 149
Ch. 9 A PLEC isoform identified in skin, muscle, and heart... 157
Ch. 10 Discussion and future perspectives... 169
Apendices... 191
Summary... 205
