Gene therapy for primary immunodeficiency

Hum Mol Genet. 2019 Oct 1;28(R1):R15-R23. doi: 10.1093/hmg/ddz170.


Gene therapy is now being trialled as a therapeutic option for an expanding number of conditions, based primarily on the successful treatment over the past two decades of patients with specific primary immunodeficiencies (PIDs) including severe combined immunodeficiency and Wiskott-Aldrich syndrome and metabolic conditions such as leukodystrophy. The field has evolved from the use of gammaretroviral vectors to more sophisticated lentiviral platforms that offer an improved biosafety profile alongside greater efficiency for hematopoietic stem cells gene transfer. Here we review more recent developments including licensing of gene therapies, use of gene corrected autologous T cells as an alternative strategy for some PIDs and the potential of targeted gene correction using various gene editing platforms. Given the promising results of recent clinical trials, it is likely that autologous gene therapies will become standard of care for a number of devastating diseases in the coming decade.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy / methods
  • Clinical Trials as Topic
  • Disease Management
  • Gene Editing
  • Genetic Predisposition to Disease
  • Genetic Therapy* / methods
  • Genetic Therapy* / trends
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Primary Immunodeficiency Diseases / genetics*
  • Primary Immunodeficiency Diseases / immunology
  • Primary Immunodeficiency Diseases / therapy*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transplantation, Autologous
  • Treatment Outcome