Unmet NeedGene therapies are regarded as a potential revolution in the health sciences and pharmaceutical fields. The number of gene therapy trials has been steadily increasing in the United States, with around 170 trials taking place in 2015. All of these trials aim to treat the causes of different diseases instead of only relieving symptoms. Many trials focus on targeting gene therapies towards the liver to cure inborn errors, such as metabolism or hemophilia, or acquired diseases, such as liver cancer and hepatitis. However, though many researchers have investigated intravascular hydrodynamic gene delivery in large animal models, translation to humans has been hampered by its technical challenges, invasiveness, and potential for significant cardiovascular complications. Thus, in order to conduct clinical trials there is a need for a safe and efficient
in vivo DNA delivery system for liver-targeted gene therapy in humans.
Technology OverviewInventors utilized intra-biliary delivery of DNA plasmids via endoscopic retrograde cholangio pancreatography (ERCP) guided hydrodynamic injection to overcome the current obstacles in liver targeted gene therapy. They divided twelve pigs into 3 groups (n = 4 per group). ERCP was performed by inflating a balloon catheter in the common hepatic duct, then creating a closed space between it and the liver parenchyma. A solution composed of plasmid/sleeping beauty (SB) mix was injected under pressure through the catheter into the closed space. Swine were sacrificed at the three different time points (21, 30, and 60 days) and liver tissue harvested. The trial was void of cardiovascular and local complications in all 12 pigs. The plasmid DNA, both single and combination, was successfully transferred into swine hepatocytes in all 12 pigs as well. In the four swine that were sacrificed at 60 days, successful genomic integration and protein expression was observed in the targeted liver tissue.
Stage of DevelopmentThe ERCP-trial is completed and other applications of ERCP are being contemplated.
