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Liver-Targeted Gene Delivery Through Retrograde Intrabiliary Infusion

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Nanotechnology for Nucleic Acid Delivery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 948))

Abstract

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.

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Author information

Authors and Affiliations

  1. Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA

    Xuan Jiang, Yong Ren & Hai-Quan Mao

  2. Translational Tissue Engineering Center and Whitaker Biomedical Engineering Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Xuan Jiang, Yong Ren & Hai-Quan Mao

  3. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    John-Michael Williford

  4. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Zhiping Li

Authors
  1. Xuan Jiang
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  2. Yong Ren
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  3. John-Michael Williford
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  4. Zhiping Li
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  5. Hai-Quan Mao
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Corresponding author

Correspondence to Hai-Quan Mao .

Editor information

Editors and Affiliations

  1. , Department of Pharmacy, Ludwig-Maximilians-University Munich, Butenandstraße 5-13, Munich, 81377, Germany

    Manfred Ogris

  2. , Department of Pharmaceutical Sciences, Wayne State University, Mack Avenue 259, Detroit, 48201, USA

    David Oupicky

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Jiang, X., Ren, Y., Williford, JM., Li, Z., Mao, HQ. (2013). Liver-Targeted Gene Delivery Through Retrograde Intrabiliary Infusion. In: Ogris, M., Oupicky, D. (eds) Nanotechnology for Nucleic Acid Delivery. Methods in Molecular Biology, vol 948. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-140-0_19

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  • DOI: https://doi.org/10.1007/978-1-62703-140-0_19

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-139-4

  • Online ISBN: 978-1-62703-140-0

  • eBook Packages: Springer Protocols

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