Genes as Medicine: The Development of Gene Therapies for Inborn Errors of Immunity

The field of gene therapy has experienced tremendous growth in the last decade ranging from improvements in the design of viral vectors for gene addition of therapeutic gene cassettes to the discovery of site-specific nucleases targeting transgenes to desired locations in the genome. Such advancements have not only enabled the development of disease models but also created opportunities for the development of tailored therapeutic approaches. There are 3 main methods of gene modification that can be used for the prevention or treatment of disease. This includes viral vector-mediated gene therapy to supply or bypass a missing/defective gene, gene editing enabled by programmable nucleases to create sequence-specific alterations in the genome, and gene silencing to reduce the expression of a gene or genes. These gene-modification platforms can be delivered either in vivo, for which the therapy is injected directed into a patient's body, or ex vivo, in which cells are harvested from a patient and modified in a laboratory setting, and then returned to the patient.