Genome editing approaches for motor neuron diseases allow permanent modification of endogenous genomic loci and correction of disease-causing mutations (e.g., SOD1, FUS and TARDBP, C9orf72), increasing the expression of therapeutic disease-modifier genes (e.g., SMN2), or reducing the expression of disease-causing gene variants (e.g., SOD1). The gene discussed is SOD1; the disease is motor neuron disorder.