Liver-targeted gene delivery through retrograde intrabiliary infusion.
Retrograde intrabiliary infusion (RII) has recently been characterized as a safe and effective administration route for liver-targeted gene delivery. Efficient transgene expression in the liver has been achieved by infusing a variety of gene vectors including adenovirus, retrovirus, lipoplexes, polyplexes, and naked DNA through the common bile duct. Here, we describe the RII technique and key infusion parameters for delivering plasmid DNA and DNA nanoparticles to the rat liver. After RII of plasmid DNA, the level of transgene expression in rat liver is comparable to that achieved by hydrodynamic injection of plasmid DNA, which is considered to be "gold standard" for liver-targeted gene delivery. RII has also been shown to significantly enhance the gene delivery efficiency by polymer/DNA nanoparticles in comparison with intravenous and intraportal infusions. This method induces minimal level of cytotoxicity and damage to the liver and bile duct. Due to these advantages, RII has the potential to be used for delivering various gene vectors in clinical setting through the endoscopic retrograde cholangiopancreatography procedure.
Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
Xuan
X
Jiang
Yong
Y
Ren
John-Michael
JM
Williford
Zhiping
Z
Li
Hai-Quan
HQ
Mao
D000818:Animals; D001659:Biliary Tract; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D018014:Gene Transfer Techniques / Q000295:instrumentation*; D007260:Infusion Pumps; D008099:Liver / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics; D008163:Luminescent Measurements; D053758:Nanoparticles / Q000737:chemistry; D010957:Plasmids / Q000235:genetics; D011108:Polymers / Q000737:chemistry; D051381:Rats; D019076:Transgenes / Q000235:genetics
D011108:Polymers; D004247:DNA; D008156:Luciferases