Targeted inversion and reversion of the blood coagulation factor 8 gene in human iPS cells using TALENs
Abstract
Hemophilia A, a genetic bleeding disorder, is often caused by chromosomal inversions that involve a portion of the blood coagulation factor VIII (F8) gene that encodes one of the key enzymes in blood clotting. In this study, we developed enzymes known as transcription activator-like effector nucleases (TALENs) that cleave chromosomal DNA in a targeted manner to invert the 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 using the same enzymes. This strategy provides an iPSC-based novel therapeutic option for the treatment of hemophilia A.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- June 2014
- DOI:
- 10.1073/pnas.1323941111
- Bibcode:
- 2014PNAS..111.9253P