Invited Reviews
Adeno-Associated Virus Vector–Based Gene Therapy for Monogenetic Metabolic Diseases of the Liver
Norman Junge,
Federico Mingozzi, Michael Ott,
Ulrich Baumann,
Norman Junge
Paediatric Gastroenterology and Hepatology, Children's Hospital, Hannover Medical School, Hannover, Germany
Search for more papers by this authorMichael Ott
Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany
Search for more papers by this authorCorresponding Author
Ulrich Baumann
Paediatric Gastroenterology and Hepatology, Children's Hospital, Hannover Medical School, Hannover, Germany
Address correspondence and reprint requests to Ulrich Baumann, MD, Hannover Medical School, Paediatric Gastroenterology and Hepatology, Carl-Neuberg-Str 1, 30625 Hannover, Germany (e-mail: [email protected]).Search for more papers by this authorNorman Junge,
Federico Mingozzi, Michael Ott,
Ulrich Baumann,
Norman Junge
Paediatric Gastroenterology and Hepatology, Children's Hospital, Hannover Medical School, Hannover, Germany
Search for more papers by this authorMichael Ott
Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany
Search for more papers by this authorCorresponding Author
Ulrich Baumann
Paediatric Gastroenterology and Hepatology, Children's Hospital, Hannover Medical School, Hannover, Germany
Address correspondence and reprint requests to Ulrich Baumann, MD, Hannover Medical School, Paediatric Gastroenterology and Hepatology, Carl-Neuberg-Str 1, 30625 Hannover, Germany (e-mail: [email protected]).Search for more papers by this authorF.M. holds patents describing the AAV technology for gene transfer to the liver and has consulted to numerous commercial entities that have developed AAV-based products. The other authors report no conflicts of interest.
ABSTRACT
Liver-based metabolic diseases account for a substantial burden of childhood diseases. In most patients, treatment is often limited to supportive measures and liver transplantation is ultimately required. Even despite the excellent long-term outcome of liver transplantation, the procedure is associated with a significant morbidity and mortality. Gene therapy, in contrast, has great potential to save lives, improve the quality of life, and offer few risks and adverse effects compared with present therapies including liver transplantation. The most promising results to date in liver gene transfer have been achieved with adeno-associated virus. Although safety issues, such as immunogenicity of vector and/or transgene product, remain an important concern, gene therapy is ready for clinical trials in adults and adolescents. Developing and testing safe approaches for efficient and long-term stable applications in newborns and small children, such as targeted integration and gene correction, is one of the remaining future challenges.
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