Liver and metabolic diseases

Liver cellThe liver is a particularly attractive target organ for the development of in vivo gene transfer strategies to treat inherited and acquired diseases. The unique features of hepatocytes, which are highly metabolically active and produce large part of the circulating proteins, the dense network of capillary vessels, which allow to reach the liver from the bloodstream and to secrete efficiently proteins back in the circulation, and the unique tolerogenic properties of the liver, have favored the development of several gene therapy approaches targeting hepatocytes. The recent demonstration of long-term correction of disease phenotype with liver gene transfer in humans further confirms the relevance of this organ as an ideal target for the development of in vivo gene therapies.

The liver and metabolic disease program at Genethon focuses on the development of in vivo therapies targeting hepatocytes with AAV vectors.

The program combines the disciplines of virology and vector design, immunology, cell biology, and basic studies on inherited diseases to develop innovative therapies aim at establishing long-lasting correction of a variety of diseases including metabolic diseases and protein deficiencies.

Our researchers were involved in some of the most exciting discoveries in the field of in vivo gene transfer and in the translation of these results to the clinic. In particular they contributed to decipher the mechanisms of transgene-specific tolerance and capsid immunogenicity in liver gene transfer. This work substantially contributed to the recent successes of human trials of liver-directed gene therapy.

The liver and metabolic disease program at Genethon takes advantage of know-how and cutting-edge vector technologies to specifically target the liver with AAV vectors. The program integrates our experience in gene transfer and immunology to develop safe and effective gene therapies for diseases affecting pediatric and adult subjects.


Currently we are moving towards the initiation of a multicenter phase I/II clinical trial of AAV vector mediated liver gene transfer for Crigler-Najjar syndrome. This program is the result of the combined efforts of several laboratories and clinical centers in Europe in close collaboration with the Patients’ Organizations.



AAV vectors, liver gene therapy, inherited diseases, tolerance induction, translational research.


SELECTED PUBLICATIONS (Link to Genethon’s publications)

  1. Nathwani et al., New England Journal of Medicine 2014
  2. Mingozzi et al., Science Translational Medicine 2013
  3. Mingozzi and High, Nature Reviews Genetics 2011
  4. Mingozzi et al., Nature Medicine 2007
  5. Mingozzi et al., Journal of Clinical Investigation 2003