Genome Editing: Breakthroughs in Double-Strand Break (DSB) Repair and What’s Next

Genome editing has revolutionized the field of genetics, offering remarkable possibilities for advancing medicine, agriculture, and microbiology.Optimizing double-stranded break (DSB) repair mechanisms is central to enhancing genome editing efficiency, which is crucial in ensuring precise gene integration.This review focuses on classical non-homologous end joining (cNHEJ), microhomology-mediated end joining (MMEJ), single-strand annealing (SSA), and homologous recombination (HR).It evaluates the current understanding of various DSB repair pathways, highlighting their strengths, limitations, and recent advancements to improve efficiency.Overall, there has been a significant enhancement in the efficiency of all four DSB repair pathways.However, we are not at a point where genome editing can be used for routine, safe medical therapy.Of the repair pathways reviewed, MMEJ emerges as the most promising due to its balanced propensity, precision, and relatively broad applicability.Lastly, while progressions on DSB-based genome editing are made, the potential benefits of switching to an alternative genome editing strategy, such as prime editor, should also be considered, which has the potential for high precision genome editing due to the avoidance of DSB creation.