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.