Next Article in Journal
Biosimilars: Company Strategies to Capture Value from the Biologics Market
Next Article in Special Issue
Current Challenges and Future Directions in Recombinant AAV-Mediated Gene Therapy of Duchenne Muscular Dystrophy
Previous Article in Journal
Mechanistic and Pharmacological Issues of Aspirin as an Anticancer Agent
Previous Article in Special Issue
Physical Factors Affecting Plasmid DNA Compaction in Stearylamine-Containing Nanoemulsions Intended for Gene Delivery
Open AccessReview

The Liver as a Target Organ for Gene Therapy: State of the Art, Challenges, and Future Perspectives

Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, Catholic University of Leuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
Author to whom correspondence should be addressed.
Pharmaceuticals 2012, 5(12), 1372-1392;
Received: 16 November 2012 / Revised: 5 December 2012 / Accepted: 6 December 2012 / Published: 10 December 2012
(This article belongs to the Special Issue Gene Therapy)
The liver is a target for gene therapy of inborn errors of metabolism, of hemophilia, and of acquired diseases such as liver cancer and hepatitis. The ideal gene transfer strategy should deliver the transgene DNA to parenchymal liver cells with accuracy and precision in the absence of side effects. Liver sinusoids are highly specialized capillaries with a particular endothelial lining: the endothelium contains open fenestrae, whereas a basal lamina is lacking. Fenestrae provide a direct access of gene transfer vectors to the space of Disse, in which numerous microvilli from parenchymal liver cells protrude. The small diameter of fenestrae in humans constitutes an anatomical barrier for most gene transfer vectors with the exception of adeno-associated viral (AAV) vectors. Recent studies have demonstrated the superiority of novel AAV serotypes for hepatocyte-directed gene transfer applications based on enhanced transduction, reduced prevalence of neutralizing antibodies, and diminished capsid immune responses. In a landmark clinical trial, hemophilia B was successfully treated with an AAV8 human factor IX expressing vector. Notwithstanding significant progress, clinical experience with these technologies remains very limited and many unanswered questions warrant further study. Therefore, the field should continue to progress as it has over the past decade, cautiously and diligently. View Full-Text
Keywords: gene transfer; liver; hepatocytes; fenestrae; AAV gene transfer; liver; hepatocytes; fenestrae; AAV
Show Figures

Figure 1

MDPI and ACS Style

Jacobs, F.; Gordts, S.C.; Muthuramu, I.; De Geest, B. The Liver as a Target Organ for Gene Therapy: State of the Art, Challenges, and Future Perspectives. Pharmaceuticals 2012, 5, 1372-1392.

Show more citation formats Show less citations formats

Article Access Map by Country/Region

Only visits after 24 November 2015 are recorded.
Back to TopTop