Over 200 retina specific genes have been associated with inherited retinal diseases (IRDs). Although genome editing represents a promising emerging field in the treatment of monogenic disorders, it relies on the capacity of the cell to repair double-strand breaks (DSB). When repairing exonic mutations or replacing exons, homology-dependent repair pathways (i.e. HDR and MMEJ) allow to preserve either the open reading frame or the splice site, whereas NHEJ will likely introduce indels. Nevertheless, HDR (G2) and MMEJ (G1) seem to be up-regulated during certain phases of the cell-cycle, whilst NHEJ is the predominant pathway at all stages in mitotic cells. Although robust data exist showing the complexity of DNA repair mechanisms and their regulation, almost nothing is known about post-mitotic neurons and photoreceptors (PRs). Transcriptome analysis is a powerful approach to study pathways activity and cell state at the same time, also using the many already published dataset. This will allow us to compare different relevant models to the human PRs bringing us to identify the most similar in terms of repair pathway activity. Further experiments will be focused on pathway manipulation, i.e. inhibiting NHEJ and boosting MMEJ. This will ultimately enabling control of DSB repair, allowing precise genome editing treatments of monogenic IRDs.