Does AAV-based gene delivery cause liver cancer? The debate heats up

Liver cancer can be triggered by mutations in cancer driver genes resulting from the insertion of adeno-associated virus (AAV) vectors used to deliver therapeutic genes, although this tumor-inducing role of AAV remains highly controversial. Recently published evidence of AAV-associated hepatocellular carcinoma was previously re-examined in Human Gene Therapy, and a new article in the Journal strongly challenges the re-interpreted data.

Jean-Charles Nault, Jessica Zucman-Rossi, INSERM, and coauthors, strongly disagree with the re-interpretation of their research, originally published in Nature Genetics, which appeared in a recent article by Kenneth Berns and colleagues in Human Gene Therapy. In the current article, "AAV2 and Hepatocellular Carcinoma", Nault et al. reaffirm their findings that insertional mutagenesis caused by AAV2 gene delivery vectors contribute to a subset of cases in rare patients. The authors also state, "we fully disagree with Berns and colleagues, who claimed a protective role for AAV infection after re-interpreting our results," emphasizing that there is no good evidence to support a tumor suppressive effect of AAV2 in human liver cells or human cancers in general.

"Our ultimate goal as translational scientists is to develop new therapies that are both safe and effective," says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Worcester, MA. "It is crucial that scientists can engage in such vigorous debates, which in turn generate interest in future studies to clarify whether or not rAAV-based holds significant cancer risk to patients. We are pleased that Human Gene Therapy can provide the forum for such debates."

Explore further

Proposed link between liver cancer and adeno-associated virus challenged in human gene therapy

More information: Jean-Charles Nault et al, AAV2 and Hepatocellular Carcinoma, Human Gene Therapy (2016). DOI: 10.1089/hum.2016.002
Journal information: Human Gene Therapy

Citation: Does AAV-based gene delivery cause liver cancer? The debate heats up (2016, May 26) retrieved 3 August 2020 from
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Feedback to editors

User comments