History of gene therapy

Gene. 2013 Aug 10;525(2):162-9. doi: 10.1016/j.gene.2013.03.137. Epub 2013 Apr 23.


Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality.

Keywords: ADA-SCID; CHMP; China's State Food and Drug Administration; Clinical trials; Committee on Human Medicinal Products; DHFR; DNA; E1; E1B 55K; EMA; Ethics; European Medicines Agency; FDA; GCV; GMP; Ganciclovir; Gene therapy; Good manufacturing practise; HAT medium; HGPRT; HSV-TK; Herpes simplex virus thymidine kinase; History; NeoR; Neomycin resistance gene; OTC; PEG-ADA; RAC; RNA; RSV; Recombinant DNA Advisory Committee; Rous sarcoma virus; SFDA; Safety; TALEN; TIL; UCLA; US Food and Drug Administration; University of California, Los Angeles; Viral vectors; ZFN; adenosine deaminase deficiency; adenoviral gene; cDNA; complementary DNA; deoxyribonucleic acid; dihydrofolate reductase; hypoxanthine and thymidine containing medium; hypoxanthine-guanine phosphoribosyl transferase; ornithine transcarbamylase; p53; polyethylene glycol adenine deaminase; protein 53, a tumour suppressor; ribonucleic acid; transcription activator-like effector nuclease; tumour-infiltrating lymphocyte; zinc finger nucleases.

Publication types

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

MeSH terms

  • China
  • European Union
  • Gene Transfer Techniques
  • Genetic Therapy / ethics
  • Genetic Therapy / history*
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Transduction, Genetic


  • Hypoxanthine Phosphoribosyltransferase