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Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells

Recently developed reprogramming and genome editing technologies make possible the derivation of corrected patient-specific pluripotent stem cell sources—potentially useful for the development of new therapeutic approaches. Starting with skin fibroblasts from patients diagnosed with cystic fibrosis,...

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Autores principales: Crane, Ana M., Kramer, Philipp, Bui, Jacquelin H., Chung, Wook Joon, Li, Xuan Shirley, Gonzalez-Garay, Manuel L., Hawkins, Finn, Liao, Wei, Mora, Daniela, Choi, Sangbum, Wang, Jianbin, Sun, Helena C., Paschon, David E., Guschin, Dmitry Y., Gregory, Philip D., Kotton, Darrell N., Holmes, Michael C., Sorscher, Eric J., Davis, Brian R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400651/
https://www.ncbi.nlm.nih.gov/pubmed/25772471
http://dx.doi.org/10.1016/j.stemcr.2015.02.005
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author Crane, Ana M.
Kramer, Philipp
Bui, Jacquelin H.
Chung, Wook Joon
Li, Xuan Shirley
Gonzalez-Garay, Manuel L.
Hawkins, Finn
Liao, Wei
Mora, Daniela
Choi, Sangbum
Wang, Jianbin
Sun, Helena C.
Paschon, David E.
Guschin, Dmitry Y.
Gregory, Philip D.
Kotton, Darrell N.
Holmes, Michael C.
Sorscher, Eric J.
Davis, Brian R.
author_facet Crane, Ana M.
Kramer, Philipp
Bui, Jacquelin H.
Chung, Wook Joon
Li, Xuan Shirley
Gonzalez-Garay, Manuel L.
Hawkins, Finn
Liao, Wei
Mora, Daniela
Choi, Sangbum
Wang, Jianbin
Sun, Helena C.
Paschon, David E.
Guschin, Dmitry Y.
Gregory, Philip D.
Kotton, Darrell N.
Holmes, Michael C.
Sorscher, Eric J.
Davis, Brian R.
author_sort Crane, Ana M.
collection PubMed
description Recently developed reprogramming and genome editing technologies make possible the derivation of corrected patient-specific pluripotent stem cell sources—potentially useful for the development of new therapeutic approaches. Starting with skin fibroblasts from patients diagnosed with cystic fibrosis, we derived and characterized induced pluripotent stem cell (iPSC) lines. We then utilized zinc-finger nucleases (ZFNs), designed to target the endogenous CFTR gene, to mediate correction of the inherited genetic mutation in these patient-derived lines via homology-directed repair (HDR). We observed an exquisitely sensitive, homology-dependent preference for targeting one CFTR allele versus the other. The corrected cystic fibrosis iPSCs, when induced to differentiate in vitro, expressed the corrected CFTR gene; importantly, CFTR correction resulted in restored expression of the mature CFTR glycoprotein and restoration of CFTR chloride channel function in iPSC-derived epithelial cells.
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spelling pubmed-44006512015-04-22 Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells Crane, Ana M. Kramer, Philipp Bui, Jacquelin H. Chung, Wook Joon Li, Xuan Shirley Gonzalez-Garay, Manuel L. Hawkins, Finn Liao, Wei Mora, Daniela Choi, Sangbum Wang, Jianbin Sun, Helena C. Paschon, David E. Guschin, Dmitry Y. Gregory, Philip D. Kotton, Darrell N. Holmes, Michael C. Sorscher, Eric J. Davis, Brian R. Stem Cell Reports Report Recently developed reprogramming and genome editing technologies make possible the derivation of corrected patient-specific pluripotent stem cell sources—potentially useful for the development of new therapeutic approaches. Starting with skin fibroblasts from patients diagnosed with cystic fibrosis, we derived and characterized induced pluripotent stem cell (iPSC) lines. We then utilized zinc-finger nucleases (ZFNs), designed to target the endogenous CFTR gene, to mediate correction of the inherited genetic mutation in these patient-derived lines via homology-directed repair (HDR). We observed an exquisitely sensitive, homology-dependent preference for targeting one CFTR allele versus the other. The corrected cystic fibrosis iPSCs, when induced to differentiate in vitro, expressed the corrected CFTR gene; importantly, CFTR correction resulted in restored expression of the mature CFTR glycoprotein and restoration of CFTR chloride channel function in iPSC-derived epithelial cells. Elsevier 2015-03-12 /pmc/articles/PMC4400651/ /pubmed/25772471 http://dx.doi.org/10.1016/j.stemcr.2015.02.005 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Report
Crane, Ana M.
Kramer, Philipp
Bui, Jacquelin H.
Chung, Wook Joon
Li, Xuan Shirley
Gonzalez-Garay, Manuel L.
Hawkins, Finn
Liao, Wei
Mora, Daniela
Choi, Sangbum
Wang, Jianbin
Sun, Helena C.
Paschon, David E.
Guschin, Dmitry Y.
Gregory, Philip D.
Kotton, Darrell N.
Holmes, Michael C.
Sorscher, Eric J.
Davis, Brian R.
Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells
title Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells
title_full Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells
title_fullStr Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells
title_full_unstemmed Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells
title_short Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells
title_sort targeted correction and restored function of the cftr gene in cystic fibrosis induced pluripotent stem cells
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400651/
https://www.ncbi.nlm.nih.gov/pubmed/25772471
http://dx.doi.org/10.1016/j.stemcr.2015.02.005
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