Gene therapy clinical trials worldwide 1989-2004-an overview

J Gene Med. 2004 Jun;6(6):597-602. doi: 10.1002/jgm.619.


In 1989, Rosenberg et al. performed the first human gene therapy trial when they used a retrovirus to introduce the gene coding for resistance to neomycin into human tumor-infiltrating lymphocytes before infusing them into five patients with advanced melanoma. This study demonstrated the feasibility of using retroviral gene transduction in humans and set the stage for further studies. Since then, over 900 clinical trials have been completed, are ongoing or have been approved worldwide. These trials have been designed to establish feasibility and safety, to demonstrate the reality of expression of therapeutic protein(s) in vivo by the genes transferred and, in some cases, to show therapeutic benefit. There is no single source of information that presents an overview of all the clinical trials undertaken worldwide. In 1997 we set up a database to bring all the information on clinical trials together as comprehensively and as globally as possible. The data were compiled and are regularly updated from official agency sources, the published literature, presentations at conferences and from information kindly provided by investigators or trial sponsors themselves. As of January 31, 2004, we have identified 918 trials in 24 countries. The USA accounts for two-thirds of these trials. Cancer is by far the most common disease indication, followed by inherited monogenic diseases, and cardiovascular diseases. Viral vectors have been the most frequently used vehicles for transferring genes into human cells, with retroviruses and adenoviruses representing the vast majority. Plasmid (naked) DNA and other non-viral vectors have been used in one-quarter of the trials. Over 100 distinct genes have been transferred. This article aims to provide a descriptive overview of the clinical trials that, to the best of our knowledge, have been or are being performed worldwide. Details of the data presented, including an interactive, searchable database that currently holds information on 918 trials, can be found on The Journal of Gene Medicine clinical trials website 1.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / therapy
  • Clinical Trials as Topic / statistics & numerical data*
  • Clinical Trials as Topic / trends
  • Enzymes / genetics
  • Genes, Tumor Suppressor
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / therapy
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Humans
  • Immunotherapy / methods
  • Neoplasms / genetics
  • Neoplasms / therapy
  • Prodrugs


  • Enzymes
  • Prodrugs