The nuclease genome editing technologies in ALL. The three most commonly used types of nucleases include programmable nucleases like Zinc Finger Nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and CRISPR systems (Clustered Regularly Interspaced Short Palindromic Repeats). These nucleases were able to induce double-strand breakgs (DSBs) in the target followed by the activation of DNA repair mechanisms . On induction of double-stranded breaks or nicks at targeted regions, repairing is done by either Non-homologous end joining (NHEJ) or Homologous recombination (HR) pathway. NHEJ is an error prone repair mechanism where joining of broken ends takes place, which generally results in heterogeneous indels (insertions and deletions) whereas HR is a precise repair method in which homologous donor template DNA is being used in repair DNA damage target site. HR is the ideal strategy for generating knock in models [81, 82].