Hepatic Gene Therapy

  • Hiroyuki Nakai
Part of the Molecular Pathology Library book series (MPLB, volume 5)


Around the turn of the new millennium, after its 20-year history, gene therapy experienced both an exciting success [1] and an unexpected failure [2, 3], which significantly changed our perspectives on gene therapy from “versatile therapy” that we expected would soon become available to cure difficult-to-treat diseases to “potentially effective therapy” that would surely be superior over conventional therapies, but still needs further refinement towards clinical applications. Since then, within less than a decade, exciting discoveries and the development of emerging technologies pertinent to gene therapy have occurred, re-inspiring a greater-than-ever interest to gene delivery approaches. As for hepatic gene transfer, we have already become able to deliver genes of interest to target cells in the liver at extremely high efficiency and with minimum toxicity, at least in mice. With the contemporary hepatic gene delivery methods in our hands, any disease can be effectively treated or even cured in animal models, as long as the right therapeutic targets have been identified in the liver. At the current stage of the development of new molecular therapeutics, in addition to seeking new breakthroughs, it is critical to further refine the technologies, to understand the underlying mechanisms of action, to explore the methods to minimize undesired reactions and side effects, and importantly to further the knowledge of disease pathogenesis. With this introduction, this chapter provides an overview of contemporary methods and applications of hepatic gene transfer with an emphasis on the underlying mechanisms of action of each gene delivery approach.


Sleep Beauty Severe Hemophilia Nonviral Vector attP Site Murine Leukemia Virus Vector 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Preparation of this chapter is in part supported by the National Institution of Health (R01 DK078388) and Cystic Fibrosis Foundation (R883-CR02). The author is most grateful to Nicole Kotchey, Frank Park and Christopher Naitza for their invaluable assistance in preparation of the manuscript.


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Microbiology and Molecular GeneticsUniversity of Pittsburgh School of MedicinePittsburghUSA

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