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Stem Cell Res. 2019 Jan;34:101349. doi: 10.1016/j.scr.2018.11.010. Epub 2019 Jan 4.

Generation of a set of isogenic, gene-edited iPSC lines homozygous for all main APOE variants and an APOE knock-out line.

Author information

1
Bioneer A/S, Kogle Alle 2, 2970 Hørsholm, Denmark. Electronic address: bsc@bioneer.dk.
2
Bioneer A/S, Kogle Alle 2, 2970 Hørsholm, Denmark.
3
Bioneer A/S, Kogle Alle 2, 2970 Hørsholm, Denmark; Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
4
Neurometabolism Research Unit, Department of Drug Design and Pharmacology, University of Copenhagen, Denmark.
5
Institute of Medical Genetics and Applied Genomics, Division of Cytogenetics, Calwerstrasse 7, University of Tuebingen, 72076, Germany.
6
Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru, Karnataka, India; University of Trans-Disciplinary Health Sciences & Technology (TDU), Bengaluru, Karnataka, India.
7
Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru, Karnataka, India.
8
Censo Biotechnologies, Edinburgh EH25 9PP, UK.
9
Janssen Research & Development, Division of Janssen Pharmaceutica; N.V., Neuroscience Therapeutic Area, Turnhoutseweg 30, 2340 Beerse, Belgium.

Abstract

Alzheimer's disease (AD) is the most frequent neurodegenerative disease amongst the elderly. The SNPs rs429358 and rs7412 in the APOE gene are the most common risk factor for sporadic AD, and there are three different alleles commonly referred to as APOE-ε2, APOE-ε3 and APOE-ε4. Induced pluripotent stem cells (iPSCs) hold great promise to model AD as such cells can be differentiated in vitro to the required cell type. Here we report the use of CRISPR/Cas9 technology employed on iPSCs from a healthy individual with an APOE-ε3/ε4 genotype to obtain isogenic APOE-ε2/ε2, APOE-ε3/ε3, APOE-ε4/ε4 lines as well as an APOE-knock-out line.

PMID:
30660866
DOI:
10.1016/j.scr.2018.11.010
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