Patients with severe congenital neutropenia (CN), an inherited pre-leukemia bone marrow failure syndrome, suffer from severe bacterial infections that usually begin shortly after birth. In addition to impaired granulopoiesis, patients with CN are at risk of myelodysplastic syndrome and acute myeloid leukemia. Most CN patients respond to daily subcutaneous injections of rhG-CSF. However, some do not, and some continue to have frequent infections despite rhG-CSF therapy. Many patients, particularly in adolescence and adulthood, experience bone pain with rhG-CSF, leading to treatment discontinuation and high risk of severe infections. The only curative treatment for CN is allogeneic hematopoietic stem cell transplantation, which is associated with severe side effects. Recent efforts by our group and others have led to the establishment of gene editing approaches aimed at correcting CN-associated mutations (e.g. in the ELANE and HAX1 genes) or inhibiting mutated genes in patients' hematopoietic stem and progenitor cells ex vivo using CRISPR/Cas gene editing. Our newly established inhibition of ELANE mRNA expression by targeting its promoter with two Cas9 nickases is also applicable to other bone marrow failure syndromes. At the current stage of clinical translation, safety criteria, desirable therapeutic thresholds, patient selection criteria and ethical considerations are important for gene therapies using CRISPR editors in patients with CN and other pre-leukemic bone marrow syndromes. We have proposed a guideline for this, which needs to be further discussed and elaborated with experts in the field.