Treating Immunodeficiency through HSC Gene Therapy

Trends Mol Med. 2016 Apr;22(4):317-327. doi: 10.1016/j.molmed.2016.02.002. Epub 2016 Mar 15.

Abstract

Haematopoietic stem cell (HSC) gene therapy has been successfully employed as a therapeutic option to treat specific inherited immune deficiencies, including severe combined immune deficiencies (SCID) over the past two decades. Initial clinical trials using first-generation gamma-retroviral vectors to transfer corrective DNA demonstrated clinical benefit for patients, but were associated with leukemogenesis in a number of cases. Safer vectors have since been developed, affording comparable efficacy with an improved biosafety profile. These vectors are now in Phase I/II clinical trials for a number of immune disorders with more preclinical studies underway. Targeted gene editing allowing precise DNA correction via platforms such as ZFNs, TALENs and CRISPR/Cas9 may now offer promising strategies to improve the safety and efficacy of gene therapy in the future.

Keywords: gene therapy; lentiviral vectors; primary immunodeficiency.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Gene Expression
  • Genetic Therapy* / methods
  • Genetic Vectors / genetics
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Immunologic Deficiency Syndromes / diagnosis
  • Immunologic Deficiency Syndromes / etiology*
  • Immunologic Deficiency Syndromes / therapy*
  • Lentivirus / genetics
  • Targeted Gene Repair / methods
  • Transduction, Genetic
  • Transgenes