“…On the other hand, a major drawback is expected, i.e., higher off-targeting effects and genotoxicity [ 40 ]. Supporting a caution in using multiplexed CRISPR-Cas9-based approaches, Samuelson et al recently reported that multiplex CRISPR-Cas9 genome editing in hematopoietic stem cells for fetal hemoglobin reinduction generates chromosomal translocations [ 40 ]. For these reasons, we therefore decided to use for HbF induction a repositioned drug, rapamycin [ 42 , 43 , 44 , 45 , 46 , 47 , 48 ], among those already validated and used in clinical trials [ 49 , 50 , 51 , 52 ].…”