Gene therapy in primary immunodeficiencies

Abstract

Primary immunodeficiencies are a group of disorders that are highly amenable to gene therapy due to their defined molecular biology and pathophysiology. The development of this new therapeutic modality has been driven by the established morbidity and mortality associated with conventional allogeneic stem cell transplantation, particularly in the human leukocyte antigen-mismatched setting. Recently, several clinical studies have demonstrated that conventional gene transfer technology can produce major beneficial therapeutic effects, but as for all cellular and pharmacologic treatment approaches, with a finite potential for toxicity. New strategies to overcome these issues are likely to establish gene therapy as an efficacious strategy for many forms of primary immunodeficiencies.

Keywords::

• γ-retrovirus
• adenosine deaminase
• chronic granulomatous disease
• hematopoietic stem cell
• insertional mutagenesis
• lentivirus
• primary immunodeficiency
• severe combined immunodeficiency
• thalassemia