Adeno-associated viruses for gene therapy – clinical implications and liver related complications, a guide for hepatologists

  • Gene therapy has garnered increasing interest over recent decades. Several therapies employing gene transfer mechanisms have been developed, and, of these, adeno-associated virus (AAV) vectors have demonstrated viability for use with in vivo gene therapy. Several AAV-based therapeutics have received regulatory approval in the last few years including those for retinal disease, spinal muscular atrophy or aromatic L-amino acid decarboxylase deficiency. Lately, with the introduction of novel liver-directed AAV vector-based therapeutics for the treatment of haemophilia A and B, gene therapy has attracted significant attention in the hepatology community, with the liver increasingly recognised as a target for gene therapy. However, the introduction of foreign DNA into hepatocytes is associated with a risk of hepatic reactions, with raised ALT (alanine aminotransferase) and AST (aspartate aminotransferase) being – so far – the most commonly reported side effects. The complete mechanisms underlying the ALT flairs remain to be determined and the long-term risks associated with these new treatments is not yet known. The liver community is increasingly being asked to support liver-directed gene therapy to mitigate potential liver associated harm. In this review, we focus on AAV vector-based gene therapy, shedding light on this promising technique and its remarkable success in haemophilia, with a special focus on hepatic complications and their management in daily clinical practice.
Metadaten
Author:Marcus Maximilian MückeORCiDGND, Sylvia FongORCiD, Graham R. FosterORCiDGND, David LillicrapORCiDGND, Wolfgang MiesbachORCiDGND, Stefan ZeuzemORCiDGND
URN:urn:nbn:de:hebis:30:3-794261
DOI:https://doi.org/https://doi.org/10.1016/j.jhep.2023.10.029
ISSN:0168-8278
Parent Title (English):Journal of hepatology
Publisher:Elsevier
Place of publication:Amsterdam u.a.
Document Type:Article
Language:English
Date of Publication (online):2024/01/24
Year of first Publication:2023
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/03/07
Tag:Adeno associated virus; Gene therapy; hemophilia; hepatitis
Volume:80
Issue:2
Page Number:10
First Page:352
Last Page:361
HeBIS-PPN:521819318
Institutes:Medizin
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0