**4. Conclusions**

Genome-editing nucleases like the popular CRISPR/Cas9 enable knockout cell lines and null zygotes to be generated by inducing site-specific DSBs within a genome. In most cases,- when a DNA template is not present, the DSB is repaired by nonhomologous end joining,- resulting in small nucleotide insertions or deletions that can be used to construct knockout alleles. However, for several reasons, these mutations do not produce the desired null- result in all cases, giving rise to a similar but functionally active protein. This undesirable- effect could limit the therapeutic efficiency of gene therapy strategies that focus on abrogating oncogene expression by CRISPR/Cas9 and should be taken in account. The use of an- sgRNA-targeting splicing site could improve the null result for *in vivo* gene therapies. This- strategy could be adopted to abrogate *in vivo* the oncogenic activity involved in tumor- maintenance.
