Gene gun bombardment with DNA-coated gold particles is a potential alternative to hydrodynamics-based transfection for delivering genes into superficial hepatocytes.

Although in vivo nonviral gene delivery to the liver is critical for hepatic gene therapy, there are a number of technical obstacles. Enhanced green fluorescent protein (EGFP)-encoding DNA was coated onto gold particles (gold–DNA), dissolved in phosphate-buffered saline (pure DNA), and prepared as a polymer adjuvant (jetPEI)–galactosidase solution (polymer–DNA). Murine liver transfection was attempted by nonviral approaches, which included hydrodynamics-based transfection (HBT) of pure DNA, transport and transhepatic injection of polymer–DNA, and gene gun bombardment with pure DNA, gold–DNA, and polymer–DNA. Only HBT and gene gun bombardment yielded significant numbers of EGFP+ hepatocytes. With the exception of the edge of the liver, HBT had a whole-liver transfection rate of 20% under optimized conditions. HBT resulted in marked hepatic infarctions, most prominently at the edge of the liver. For gene gun bombardment, the transfection rate was pressure dependent and limited to 15% for gold–DNA. Triple or...