Balloon Catheter Delivery of Helper-dependent Adenoviral Vector Results in Sustained, Therapeutic hFIX Expression in Rhesus Macaques

Transgene Expression up to 7 Years in Nonhuman Primates Following Hepatic Transduction with Helper-Dependent Adenoviral Vectors

“…For example, a single injection of HDAd into rodents can result in lifelong hepatic transgene expression, which is about 2 years (Kim et al, 2001;Toietta et al, 2005). Similarly, in nonhuman primates, we have demonstrated that hepatic transduction by HDAd can also provide up to 2.6 years of high-level transgene expression (Brunetti-Pierri et al, 2006, 2007, 2009, 2012. In addition, hepatic transgene expression for up to 2 years has been reported in the dog following a single injection of HDAd (Brunetti-Pierri et al, 2005a;McCormack et al, 2006).…”

“Evolving nanoparticle gene delivery vectors for the liver: What has been learned in 30 years”

“…Hydrodynamic delivery is safe for use in mice [48,49], but adapting the method for use in larger animals is more complicated. By surgically isolating the liver from the rest of the circulation, the volumes needed to achieve hydrodynamic pressures are greatly reduced, allowing the method to be used on dogs [50], pigs [51], and nonhuman primates [52], with the potential to be adapted for the safe delivery to the liver of humans.…”

Adenoviral Vectors for Hemophilia Gene Therapy

“…This resulted in up to 80-fold improvement in hepatic transduction compared to systemic vector injection and with transgene expression sustained for up to 2.6 years [46]. This balloon catheter method was used to deliver a low dose of HDAd expression hFIX into rhesus macaques which can result in therapeutic levels of hFIX expression for up to 2.8 years post-injection ( Figure 3B) [47].…”