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Constitutive and Inducible Systems for Genetic In Vivo Modification of Mouse Hepatocytes Using Hydrodynamic Tail Vein Injection
Published on: February 2, 2018
Hydrodynamics based transfection in normal and fibrotic rats
Rita Yeikilis1, Shunit Gal, Natalia Kopeiko
1Department of Anatomy and Cell Biology, Faculty of Medicine, POB 9649, Haifa 31096, Israel.
World Journal of Gastroenterology
|October 13, 2006
Summary
Hydrodynamics based transfection (HBT) creates gaps in liver cells, aiding DNA transfer but not guaranteeing gene expression. Reducing fibrosis improves HBT efficacy in fibrotic rats.
Area of Science:
- Gene therapy
- Molecular biology
- Hepatology
Background:
- Hydrodynamics based transfection (HBT) is a common in vivo gene delivery method for liver cells.
- The precise mechanism of HBT-mediated gene transfection remains unclear.
- Understanding HBT is crucial for optimizing gene therapy strategies.
Purpose of the Study:
- To elucidate the mechanism of gene transfection via HBT.
- To investigate the role of endothelial gaps in HBT.
- To assess HBT efficiency in fibrotic liver models.
Main Methods:
- Luciferase plasmid injection into rats using HBT.
- Utilizing scanning and transmission electron microscopy.
- Employing Halofuginone to inhibit collagen synthesis in fibrotic rats.
Main Results:
- HBT induced significant endothelial gaps within minutes, which resolved over 10 days.
- Endothelial gaps alone were insufficient for efficient gene expression.
- Transfection efficiency in fibrotic rats was reduced and improved by Halofuginone treatment.
Conclusions:
- HBT-induced endothelial gaps facilitate DNA molecule transfer but do not ensure hepatocyte transfection.
- Fibrosis diminishes HBT efficiency, but this can be mitigated by reducing extracellular matrix (ECM) load.
- HBT is a viable method for fibrotic rat livers if ECM accumulation is addressed.
