Efficient liver gene transfer with foamy virus vectors.

Area of Science:

• Hepatology
• Gene Therapy
• Viral Vector Technology

Background:

• Liver gene transfer holds promise for treating genetic and acquired disorders.
• Hydrodynamic gene transfer (HGT) is an effective method for achieving gene delivery in large animals.

Purpose of the Study:

• To compare the liver gene transfer efficiency of foamy virus (FV) vectors versus naked plasmids using HGT in pigs.
• To assess the persistence of gene expression mediated by these vectors.

Main Methods:

• HGT was administered to four juvenile pigs using identical plasmid backbones, either as naked DNA or as FV vector particles.
• Gene transfer efficiency and expression persistence were evaluated at 1 week and 1 month post-infusion via PCR and real-time PCR.

Main Results:

• HGT was well-tolerated with no adverse events.
• Naked plasmid DNA was undetectable at 1 week, with minimal presence at 1 month.
• FV vectors resulted in positive vector sequences in 64.3% of liver samples at 1 month, with significant expression levels relative to GAPDH.

Conclusions:

• Foamy virus (FV) vectors facilitate medium-term therapeutic gene expression in the liver.
• The efficacy of FV vectors is attributed to the HGT procedure and the inherent tropism of FV for hepatocytes.