Biallelic rescue of CTG18.1 in two Fuchs endothelial corneal dystrophy–derived iPSC lines (SCTCi047-A-2, SCTCi046-A-2) following a two-step gene editing strategy

Elisa Landi; Ellen van Beusekom; Shifra Ben-Dor; Silvia Albert; Mor M. Dickman; Vanessa L.S. LaPointe; Hans van Bokhoven

doi:10.1016/j.scr.2026.104032

Biallelic rescue of CTG18.1 in two Fuchs endothelial corneal dystrophy–derived iPSC lines (SCTCi047-A-2, SCTCi046-A-2) following a two-step gene editing strategy

Elisa Landi^*
, Ellen van Beusekom
, Shifra Ben-Dor
, Silvia Albert
, Mor M. Dickman
, Vanessa L.S. LaPointe
, Hans van Bokhoven

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Fuchs endothelial corneal dystrophy (FECD) is an age-related condition distinguished by the degeneration of the corneal endothelium. An intronic CTG18.1 repeat in the transcription factor 4 (TCF4) gene has been associated with a 78-fold increased risk of developing the disease when at least one copy of the CTG18.1 expands above 50 repeats. Employing patient-derived material, we applied a dual CRISPR/Cas9-mediated editing approach to rescue the expansion. Combining non-homologous end-joining (NHEJ) and homologous direct repair (HDR) events, we generated two FECD-derived ^+/+(CTG)₈ induced pluripotent stem cell (iPSC) lines, which were then successfully characterized, providing relevant isogenic controls for disease-modelling purposes.

Original language	English
Article number	104032
Journal	Stem Cell Research
Volume	95
DOIs	https://doi.org/10.1016/j.scr.2026.104032
Publication status	Published - Sept 2026

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1-s2.0-S1873506126001285-mainFinal published version, 2.2 MBLicence: CC BY

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@article{7c0508a301774b9fb580b84f8775a5e6,

title = "Biallelic rescue of CTG18.1 in two Fuchs endothelial corneal dystrophy–derived iPSC lines (SCTCi047-A-2, SCTCi046-A-2) following a two-step gene editing strategy",

abstract = "Fuchs endothelial corneal dystrophy (FECD) is an age-related condition distinguished by the degeneration of the corneal endothelium. An intronic CTG18.1 repeat in the transcription factor 4 (TCF4) gene has been associated with a 78-fold increased risk of developing the disease when at least one copy of the CTG18.1 expands above 50 repeats. Employing patient-derived material, we applied a dual CRISPR/Cas9-mediated editing approach to rescue the expansion. Combining non-homologous end-joining (NHEJ) and homologous direct repair (HDR) events, we generated two FECD-derived +/+(CTG)8 induced pluripotent stem cell (iPSC) lines, which were then successfully characterized, providing relevant isogenic controls for disease-modelling purposes.",

author = "Elisa Landi and \{van Beusekom\}, Ellen and Shifra Ben-Dor and Silvia Albert and Dickman, \{Mor M.\} and LaPointe, \{Vanessa L.S.\} and \{van Bokhoven\}, Hans",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/",

year = "2026",

month = sep,

doi = "10.1016/j.scr.2026.104032",

language = "English",

volume = "95",

journal = "Stem Cell Research",

issn = "1873-5061",

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TY - JOUR

T1 - Biallelic rescue of CTG18.1 in two Fuchs endothelial corneal dystrophy–derived iPSC lines (SCTCi047-A-2, SCTCi046-A-2) following a two-step gene editing strategy

AU - Landi, Elisa

AU - van Beusekom, Ellen

AU - Ben-Dor, Shifra

AU - Albert, Silvia

AU - Dickman, Mor M.

AU - LaPointe, Vanessa L.S.

AU - van Bokhoven, Hans

PY - 2026/9

Y1 - 2026/9

N2 - Fuchs endothelial corneal dystrophy (FECD) is an age-related condition distinguished by the degeneration of the corneal endothelium. An intronic CTG18.1 repeat in the transcription factor 4 (TCF4) gene has been associated with a 78-fold increased risk of developing the disease when at least one copy of the CTG18.1 expands above 50 repeats. Employing patient-derived material, we applied a dual CRISPR/Cas9-mediated editing approach to rescue the expansion. Combining non-homologous end-joining (NHEJ) and homologous direct repair (HDR) events, we generated two FECD-derived +/+(CTG)8 induced pluripotent stem cell (iPSC) lines, which were then successfully characterized, providing relevant isogenic controls for disease-modelling purposes.

AB - Fuchs endothelial corneal dystrophy (FECD) is an age-related condition distinguished by the degeneration of the corneal endothelium. An intronic CTG18.1 repeat in the transcription factor 4 (TCF4) gene has been associated with a 78-fold increased risk of developing the disease when at least one copy of the CTG18.1 expands above 50 repeats. Employing patient-derived material, we applied a dual CRISPR/Cas9-mediated editing approach to rescue the expansion. Combining non-homologous end-joining (NHEJ) and homologous direct repair (HDR) events, we generated two FECD-derived +/+(CTG)8 induced pluripotent stem cell (iPSC) lines, which were then successfully characterized, providing relevant isogenic controls for disease-modelling purposes.

UR - https://www.scopus.com/pages/publications/105041923328

U2 - 10.1016/j.scr.2026.104032

DO - 10.1016/j.scr.2026.104032

M3 - Article

AN - SCOPUS:105041923328

SN - 1873-5061

VL - 95

JO - Stem Cell Research

JF - Stem Cell Research

M1 - 104032

ER -

Biallelic rescue of CTG18.1 in two Fuchs endothelial corneal dystrophy–derived iPSC lines (SCTCi047-A-2, SCTCi046-A-2) following a two-step gene editing strategy

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