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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
Enhanced transgene expression from chromatinized plasmid DNA in mouse liver
Hiroyuki Kamiya1, Shiho Miyamoto, Hitomi Goto
1Graduate School of Science and Engineering, Ehime University, Matsuyama 790-8577, Japan. hirokam@ehime-u.ac.jp
International Journal of Pharmaceutics
|December 19, 2012
Summary
Chromatinizing plasmid DNA with histones enhances transgene expression in mouse liver. Using acetylation-enriched histones further boosts this efficiency for effective in vivo gene delivery.
Area of Science:
- Molecular Biology
- Gene Therapy
- Epigenetics
Background:
- Plasmid DNA is a common tool for gene delivery.
- Gene expression efficiency can be limited by DNA delivery methods.
- Chromatin structure influences DNA accessibility and gene expression.
Purpose of the Study:
- To investigate the efficiency of chromatinized plasmid DNA for in vivo transgene expression.
- To compare the efficacy of naked plasmid DNA versus chromatinized plasmid DNA.
- To evaluate the impact of histone acetylation on transgene expression.
Main Methods:
- In vitro chromatinization of plasmid DNA with core histones (H2A, H2B, H3, H4).
- Hydrodynamics-based administration of plasmid DNA into mouse liver.
- Comparison of transgene expression levels between naked and chromatinized DNA.
- Utilizing acetylation-enriched histones from trichostatin A-treated cells.
Main Results:
- Chromatinized plasmid DNA showed more efficient transgene expression than naked DNA.
- Acetylation-enriched histones led to even greater transgene expression efficiency.
- Hydrodynamics-based delivery facilitated efficient in vivo gene expression from chromatinized DNA.
Conclusions:
- Chromatinized plasmid DNA is a superior method for efficient in vivo transgene expression.
- Histone acetylation plays a crucial role in enhancing gene expression from delivered DNA.
- This approach holds promise for advanced gene therapy applications.
