Gene therapy for primary immunodeficiencies: up-to-date.

ABSTRACT

INTRODUCTION: Primary immunodeficiencies (PIDs) are monogenic disorders of the immune system associated with increased susceptibility to life-threatening infection. Curative treatment has been limited to hematopoietic stem cell transplant (HSCT), however toxic immunosuppression, graft failure, and graft versus host disease greatly reduce overall survival rates. Gene therapy is a targeted curative therapy that reduces these risks by utilizing autologous hematopoietic stem cells. The treatment has found significant success and is anticipated to become the standard of care in a number of PIDs. AREAS COVERED This review is a summary of the developments in gene therapy, gene editing, and current gene therapy approaches in specific PIDs. EXPERT OPINION The field of gene therapy has rapidly developed over the last three decades, with the first licensed pharmaceutical gene therapy product now available. After initial clinical trials discovered serious adverse events in the form of insertional oncogenesis, significant improvements in vector design have made the treatment a viable curative therapy. Cryopreservation has expanded the scope of gene therapy by increasing accessibility of the product to wider geographic locations. Targeted gene editing using engineered nucleases, while still in early stages of development, will further add to the repertoire of potential treatments available for PIDs.