Cover Page
The following handle holds various files of this Leiden University dissertation:
http://hdl.handle.net/1887/62204
Author: Chen, X.
Title: Determinants of genome editing outcomes: the impact of target and donor DNA structures
Issue Date: 2018-05-16
Determinants of genome editing outcomes:
the impact of target and donor DNA structures
Xiaoyu Chen
ISBN: 978-94-6332-349-9
© Xiaoyu Chen, 2018, Leiden, the Netherlands. All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means without prior written permission of the author.
Cover: concept and design by Xiaoyu Chen. Digital rain, Cas9 sequence.
The printing of this thesis was supported by the Virus and Stem Cell group, De- partment of Cell and Chemical Biology, Leiden University Medical Center.
Printed by GVO drukkers & vormgevers B.V. (www.proefschriften.nl)
Determinants of genome editing outcomes:
the impact of target and donor DNA structures
Proefschrift ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties te verdedigen op woensdag 16 mei 2018
klokke 13:45 uur
door
Xiaoyu Chen
Geboren te Xingtai, Hebei, China
in 1990
Promotor: Prof. Dr. R.C. Hoeben Co-promotor: Dr. M.A.F.V. Gonçalves
Leden promotiecommissie:
Prof. Dr. M. Tijsterman
Prof. Dr. A. Schambach (Hannover Medical School) Prof. Dr. S.M. van der Maarel
Prof. Dr. R. Kühn (Max Delbrück Center for Molecular Medicine) Dr. M.E. Ressing
The research presented in this thesis was performed at the Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands. This research was in part supported by the Dutch Prinses Be- atrix Spierfonds (W.OR11-18), the French AFM-Téléthon (grant number 16621), and the China Scholarship Council.
谨以此书献给爸爸，妈妈和弟弟
以及恩师李春岩
To my mom, dad and brother,
and Chunyan Li
CONTENTS
General Introduction /
009Chapter 1 CRISPR-Cas9 Genome Editing, Five Years on / 013 Chapter 2 In trans Paired Nicking Triggers Seamless Genome Editing without Double-stranded DNA Cutting / 031 Chapter 3 Probing the Impact of Chromatin Conformation on Genome Editing Tools / 061
Chapter 4 The chromatin Structure Differentially Impacts
High-specificity CRISPR-Cas9 Nuclease Strategies / 081
Chapter 5 The Chromatin Structure Governs Gene-editing Outcomes / 093
Chapter 6 Engineered Viruses as Genome Editing Devices / 119 Chapter 7 The Emerging Role of Viral Vectors as Vehicles for DMD Gene Editing / 143
