Perspectives on gene therapy for Fanconi anemia

Introduction: Fanconi anemia (FA) is a rare inherited disease characterized by congenital abnormalities, bone marrow failure (BMF) and cancer predisposition. Although allogeneic hematopoietic stem cell transplantation (HSCT) is the preferential therapy for restoring the bone marrow (BM) function of FA patients, gene therapy represents a new alternative in FA.Areas covered: This review covers the areas of gene therapy with γ-retroviral and lentiviral vectors. Additionally, the perspectives of gene editing and cell reprogramming for the gene therapy of FA are discussed.Expert opinion: Currently, there is no clinical evidence showing that gene therapy can restore the BM function of FA patients. However, improvements in vector development and advances in manipulation of hematopoietic stem cells (HSCs) have resulted in gene therapy progresses, opening new perspectives for the treatment of FA patients. Although, in FA patients, reduced HSC numbers will be available for gene correction and autologous transplantation, a strong selective advantage is expected from corrected FA HSCs. This suggests that limited numbers of corrected HSCs could be sufficient to rescue the hematopoiesis of FA patients. In addition to ex vivo gene therapy, significant advances have been achieved in in vivo gene therapy and also in the fields of gene targeting and cell reprogramming, with a potential role in the future treatment of FA.