Generation and precise genetic correction of patient-derived hiPSCs have great 
potential in regenerative medicine. Such targeted genetic manipulations can now 
be achieved using gene-editing nucleases. Here, we report generation of cystic 
fibrosis (CF) and Gaucher's disease (GD) hiPSCs respectively from CF (homozygous 
for CFTRΔF508 mutation) and Type II GD [homozygous for β-glucocerebrosidase 
(GBA) 1448T>C mutation] patient fibroblasts, using CCR5- specific TALENs. 
Site-specific addition of loxP-flanked Oct4/Sox2/Klf4/Lin28/Nanog/eGFP gene 
cassette at the endogenous CCR5 site of patient-derived disease-specific primary 
fibroblasts induced reprogramming, giving rise to both monoallele (heterozygous) 
and biallele CCR5-modified hiPSCs. Subsequent excision of the donor cassette was 
done by treating CCR5-modified CF and GD hiPSCs with Cre. We also demonstrate 
site-specific correction of sickle cell disease (SCD) mutations at the 
endogenous HBB locus of patient-specific hiPSCs [TNC1 line that is homozygous 
for mutated β- globin alleles (βS/βS)], using HBB-specific TALENs. SCD-corrected 
hiPSC lines showed gene conversion of the mutated βS to the wild-type βA in one 
of the HBB alleles, while the other allele remained a mutant phenotype. After 
excision of the loxP-flanked DNA cassette from the SCD-corrected hiPSC lines 
using Cre, we obtained secondary heterozygous βS/βA hiPSCs, which express the 
wild-type (βA) transcript to 30-40% level as compared to uncorrected (βS/βS) SCD 
hiPSCs when differentiated into erythroid cells. Furthermore, we also show that 
TALEN-mediated generation and genetic correction of disease-specific hiPSCs did 
not induce any off-target mutations at closely related sites.