Safety of gene therapy: New insights to a puzzling case

Michael Rothe, Axel Schambach, Luca Biasco

Research output: Contribution to journalArticlepeer-review


Over the last few years, the transfer of therapeutic genes via gammaretro- or lentiviral vector systems has proven its virtue as an alternative treatment for a series of genetic disorders. The number of approved phase I/II clinical trials, especially for rare diseases, is steadily increasing, but the overall hurdles to become a broadly acceptable therapy remain numerous. The efforts by clinicians and basic scientists have tremendously improved the knowledge available about feasibility and biosafety of gene therapy. Nonetheless, despite the generation of a plethora of clinical and preclinical safety data, we still lack sufficiently powerful assays to predictively assess the exact levels of toxicity that might be observed in any given clinical gene therapy. Insertional mutagenesis is one of the major concerns when using integrating vectors for permanent cell modification, and the occurrence of adverse events related to genotoxicity, in early gene therapy trials, has refrained the field of gene therapy from emerging further. In this review, we provided a comprehensive overview on the basic principles and potential co-factors concurring in the generation of adverse events reported in gene therapy clinical trials using integrating vectors. Additionally, we summarized the available systems to assess genotoxicity at the preclinical level and we shed light on the issues affecting the predictive value of these assays when translating their results into the clinical arena. In the last section of the review we briefly touched on the future trends and how they could increase the safety of gene therapy employing integrating vector technology to take it to the next level.

Original languageEnglish
Pages (from-to)429-436
Number of pages8
JournalCurrent Gene Therapy
Issue number6
Publication statusPublished - Jan 1 2014


  • Clinical trials
  • Gene therapy
  • Insertional mutagenesis
  • Lentiviral
  • Preclinical
  • Retroviral
  • Safety

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)
  • Drug Discovery
  • Medicine(all)


Dive into the research topics of 'Safety of gene therapy: New insights to a puzzling case'. Together they form a unique fingerprint.

Cite this