구본경 (University Medical Center Utrecht, Hubrecht Institute, 현 University of Cambridge) | 한빛사논문 > 한빛사

한빛사논문, 상위피인용논문

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University Medical Center Utrecht, Hubrecht Institute, 현 University of Cambridge

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Cell Stem Cell, Volume 13, Issue 6, 653-658, 5 December 2013 | http://dx.doi.org/10.1016/j.stem.2013.11.002 Functional Repair of CFTR by CRISPR/Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients

Abstract

Gerald Schwank^{1, 2, 7}, Bon-Kyoung Koo^{1, 2, 7, 8}, Valentina Sasselli^{1, 2}, Johanna F. Dekkers^{3, 4}, Inha Heo^{1, 2}, Turan Demircan¹, Nobuo Sasaki^{1, 2}, Sander Boymans¹, Edwin Cuppen^{1, 6}, Cornelis K. van der Ent³, Edward E.S. Nieuwenhuis⁵, Jeffrey M. Beekman^{5, 6}, Hans Clevers^{1, 2, *}

¹ Hubrecht Institute/KNAW, Uppsalalaan 8, Utrecht 3584 CT, The Netherlands
² University Medical Center Utrecht, Uppsalalaan 8, Utrecht 3584 CT, The Netherlands
³ Department of Pediatric Pulmonology, Wilhelmina Children’s Hospital, University Medical Center, Lundlaan 6, Utrecht 3584 EA, The Netherlands
⁴ Department of Immunology, Wilhelmina Children’s Hospital, University Medical Center, Lundlaan 6, Utrecht 3584 EA, The Netherlands
⁵ Department of Pediatric Gastroenterology, Wilhelmina Children’s Hospital, University Medical Center, Lundlaan 6, Utrecht 3584 EA, The Netherlands
⁶ Department of Medical Genetics, UMC Utrecht, Universiteitsweg 100, Utrecht 3584 GG, The Netherlands
⁷ These authors contributed equally to this work
⁸ Present address: Wellcome Trust: Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK

^*Corresponding author : Hans Clevers

Summary
Single murine and human intestinal stem cells can be expanded in culture over long time periods as genetically and phenotypically stable epithelial organoids. Increased cAMP levels induce rapid swelling of such organoids by opening the cystic fibrosis transmembrane conductor receptor (CFTR). This response is lost in organoids derived from cystic fibrosis (CF) patients. Here we use the CRISPR/Cas9 genome editing system to correct the CFTR locus by homologous recombination in cultured intestinal stem cells of CF patients. The corrected allele is expressed and fully functional as measured in clonally expanded organoids. This study provides proof of concept for gene correction by homologous recombination in primary adult stem cells derived from patients with a single-gene hereditary defect.

논문정보

형식Research article
게재일2013년 12월 (BRIC 등록일 2013-12-06)
연구진국외 연구진
분야 생명과학 > 노화/암생물학
피인용횟수60회 이상 인용된 논문 (상위피인용논문 등록일 2016-12-31)

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