Targeted inversion and reversion of the blood coagulation factor 8 gene in iPS cells using TALENs

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Title
Targeted inversion and reversion of the blood coagulation factor 8 gene in iPS cells using TALENs
Author(s)
Chul-Yong Park; Jungeun Kim; Jiyeon Kweon; Jeong Sang Son; Jae Souk Lee; Jeong-Eun Yoo; Sung-Rae Cho; Jong-Hoon Kim; Jin-Soo Kim; Dong-Wook Kim
Publication Date
2014-06
Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.111, no.25, pp.9253 - 9258
Publisher
NATL ACAD SCIENCES
Abstract
Hemophilia A, one of the most common genetic bleeding disorders, is caused by various mutations in the blood coagulation factor VIII (F8) gene. Among the genotypes that result in hemophilia A, two different types of chromosomal inversions that involve a portion of the F8 gene are most frequent, accounting for almost half of all severe hemophilia A cases. In this study, we used a transcription activator-like effector nuclease (TALEN) pair to invert a 140-kbp chromosomal segment that spans the portion of the F8 gene in human induced pluripotent stem cells (iPSCs) to create a hemophilia A model cell line. In addition, we reverted the inverted segment back to its normal orientation in the hemophilia model iPSCs using the same TALEN pair. Importantly, we detected the F8 mRNA in cells derived from the reverted iPSCs lines, but not in those derived from the clones with the inverted segment. Thus, we showed that TALENs can be used both for creating disease models associated with chromosomal rearrangements in iPSCs and for correcting genetic defects caused by chromosomal inversions. This strategy provides an iPSC-based novel therapeutic option for the treatment of hemophilia A and other genetic diseases caused by chromosomal inversions.
URI
https://pr.ibs.re.kr/handle/8788114/1509
ISSN
0027-8424
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > Journal Papers (저널논문)
Files in This Item:
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