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Seamless correction of the sickle cell disease mutation of the HBB gene in human induced pluripotent stem cells using TALENs
Author(s) -
Sun Ning,
Zhao Huimin
Publication year - 2014
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.25018
Subject(s) - transcription activator like effector nuclease , induced pluripotent stem cell , genome editing , biology , zinc finger nuclease , genetics , gene , genetic enhancement , effector , gene targeting , mutation , computational biology , crispr , embryonic stem cell , microbiology and biotechnology
Sickle cell disease (SCD) is the most common human genetic disease which is caused by a single mutation of human β‐globin ( HBB ) gene. The lack of long‐term treatment makes the development of reliable cell and gene therapies highly desirable. Disease‐specific patient‐derived human induced pluripotent stem cells (hiPSCs) have great potential for developing novel cell and gene therapies. With the disease‐causing mutations corrected in situ, patient‐derived hiPSCs can restore normal cell functions and serve as a renewable autologous cell source for the treatment of genetic disorders. Here we successfully utilized transcription activator‐like effector nucleases (TALENs), a recently emerged novel genome editing tool, to correct the SCD mutation in patient‐derived hiPSCs. The TALENs we have engineered are highly specific and generate minimal off‐target effects. In combination with piggyBac transposon, TALEN‐mediated gene targeting leaves no residual ectopic sequences at the site of correction and the corrected hiPSCs retain full pluripotency and a normal karyotype. Our study demonstrates an important first step of using TALENs for the treatment of genetic diseases such as SCD, which represents a significant advance toward hiPSC‐based cell and gene therapies. Biotechnol. Biotechnol. Bioeng. 2014;111: 1048–1053. © 2013 Wiley Periodicals, Inc.