Gene therapy and genome editing for primary immunodeficiency diseases

Abstract

In past two decades the gene therapy using genetic modified autologous hematopoietic stem cells (HSCs) transduced with the viral vector has become a promising alternative option for treating primary immunodeficiency diseases (PIDs). Despite of some pitfalls at early stage clinical trials, the field of gene therapy has advanced significantly in the last decade with improvements in viral vector safety, preparatory regime for manufacturing high quality virus, automated CD34 cell purification. Hence, the overall outcome from the clinical trials for the different PIDs has been very encouraging. In addition to the viral vector based gene therapy, the recent fast moving forward developments in genome editing using engineered nucleases in HSCs has provided a new promising platform for the treatment of PIDs. This review provides an overall outcome and progress in gene therapy clinical trials for SCID-X, ADA-SCID, WAS, X- CGD, and the recent developments in genome editing technology applied in HSCs for developing potential therapy, particular in the key studies for PIDs.

Keywords: Adenosine deaminase deficient; Chronic granulomatous disease; Gene therapy; Genome editing; Hematopoietic progenitor stem cells; Primary immunodeficiency diseases; Wiskott-Aldrich syndrome; X-liked severe combined immunodeficiency.