Article

High volume naked DNA tail-vein injection restores liver function in Fah-knock out mice

Department of Surgery, University Medical Center Regensburg, Regensburg, Germany.
Journal of Gastroenterology and Hepatology (Impact Factor: 3.33). 05/2010; 25(5):1002-8. DOI: 10.1111/j.1440-1746.2009.06156.x
Source: PubMed

ABSTRACT Despite pharmaceutical treatment with NTBC (2-2-nitro-4-fluoromethylbenzoyl-1,3-cyclohexanedione), a high incidence of liver malignancies occur in humans and mice suffering from hereditary tyrosinemia type 1 (HT1) caused by mutation of the fumarylacetoacetate hydrolase (fah) gene.
To evaluate the efficacy of a definitive treatment for HT1, we transfected fah knockout mice with naked plasmid DNA using high volume tail-vein injection. This approach was chosen to reduce the occurrence of insertional mutagenesis that is frequently observed when using other (retro-)viral vectors. To prolong gene expression, the fah gene was cloned between adeno-associated virus (AAV)-specific inverted terminal repeats (ITRs).
All animals treated with high volume plasmid DNA injections could be successfully weaned off NTBC and survived in the long term without any further pharmacological support. Up to 50% fah positive hepatocytes were detected in livers of naked plasmid DNA-treated animals and serum liver function tests approximated those of wild-type controls.
Naked plasmid DNA transfection offers a promising alternative treatment for HT1. Minimizing side-effects makes this approach especially appealing.

0 Bookmarks
 · 
132 Views
  • Source
    Journal of Gastroenterology and Hepatology 05/2010; 25(5):848-50. DOI:10.1111/j.1440-1746.2010.06313.x · 3.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The hydrodynamic tail vein injection is a technique that is used to deliver nucleic acids into live mice. Delivery through this method results in the in vivo transfection of foreign DNA primarily in the liver. Here, we describe the use of this technique to test for regulatory activity of liver promoters and enhancers, using a dual luciferase reporter system as the readable/measureable output and how this application can be used for pharmacogenomic studies.
    Methods in molecular biology (Clifton, N.J.) 01/2013; 1015:279-89. DOI:10.1007/978-1-62703-435-7_18 · 1.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Liver based metabolic disorders account for 10 to 15% of the indications for paediatric liver transplantation. In the last three decades, important progress has been made in the understanding of these diseases, and new therapies have emerged. Concomitantly, medical and surgical innovations have lead to improved results of paediatric liver transplantation, patient survival nowadays exceeding 80% 10 year after surgery with close to normal quality of life in most survivors. This review is a practical update on medical therapy, indications and results of liver transplantation, and potential future therapies, for the main liver based metabolic disorders in which paediatric liver transplantation may be considered. Part 1 focuses on metabolic based liver disorders without liver lesions, and part 2 on metabolic liver diseases with liver lesions.
    Gastroentérologie Clinique et Biologique 03/2011; 35(4):271-80. DOI:10.1016/j.clinre.2011.01.008 · 0.80 Impact Factor