Liver-targeted gene delivery through retrograde intrabiliary infusion

Area of Science:

• Hepatology
• Gene Therapy
• Nanomedicine

Background:

• Retrograde intrabiliary infusion (RII) is an emerging route for liver-targeted gene delivery.
• Various gene vectors, including viral and non-viral types, have been successfully delivered via RII through the common bile duct.
• RII has demonstrated potential for efficient gene transfer to hepatocytes.

Purpose of the Study:

• To describe the RII technique and critical parameters for delivering plasmid DNA and DNA nanoparticles to rat liver.
• To evaluate the efficiency of RII for liver gene delivery compared to established methods.
• To assess the safety profile of RII in terms of liver and bile duct toxicity.

Main Methods:

• Detailed description of the RII procedure in rats.
• Administration of plasmid DNA and polymer/DNA nanoparticles via RII.
• Comparison of RII with hydrodynamic injection, intravenous, and intraportal infusion methods.
• Assessment of transgene expression levels and liver/bile duct cytotoxicity.

Main Results:

• RII achieved transgene expression levels in rat liver comparable to hydrodynamic injection.
• RII significantly enhanced gene delivery efficiency for polymer/DNA nanoparticles compared to intravenous and intraportal routes.
• The RII method exhibited minimal cytotoxicity and damage to the liver and bile duct.

Conclusions:

• RII is a safe and effective method for liver-targeted gene delivery in rats.
• RII offers an alternative to hydrodynamic injection with comparable efficiency and improved safety.
• The RII technique holds promise for clinical applications in gene therapy via endoscopic retrograde cholangiopancreatography.