09 June 2021
Vol 13, Issue 597

About The Cover

Cover image expansion

ONLINE COVER Therapeutic Toxicity. The image shows a liver section from an acetaminophen-treated mouse expressing acetaminophen-metabolizing Cyp2E1 (green) and its cofactor Cypor (red). Genome-integrating gene therapy vectors promise stable therapeutic effects, but integration is difficult to achieve in hepatocytes. Vonada et al. developed an adenoviral vector containing a shRNA against Cypor. In this system, successful integration selectively protected the resulting transgene-expressing hepatocytes, but not non-integrated hepatocytes, against toxic drug exposure. Administration of the vector plus a moderately hepatotoxic dose of acetaminophen to neonatal mice selected for transgene-expressing cells and achieved therapeutic viral vector integration in models of hemophilia B and phenylketonuria, suggesting the potential of the approach for gene therapy for liver diseases. [CREDIT: VONADA ET AL./SCIENCE TRANSLATIONAL MEDICINE]