Efficient and durable transgene expression systems

2015 Fiscal Year Final Research Report

• Project/Area Number: 25282144
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Hiroshima University (2014-2015); Ehime University (2013)
• Principal Investigator: Kamiya Hiroyuki 広島大学, 医歯薬保健学研究院(薬), 教授 (10204629)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 遺伝子治療 / プラスミドDNA

Outline of Final Research Achievements

Histone acetylation is associated with activation of genes on chromosomes. Transgene expression from plasmid DNA might be increased when histone bound to plasmid DNA is acetylated. We employed the positive feedback system using a fusion protein of the sequence-specific DNA binding domain of yeast GAL4 and the histone acetyltransferase (HAT) domain of mouse CREB-binding protein (GAL4-HAT), in which GAL4-HAT promotes its own expression as well as that of a reporter gene product (luciferase), to examine the hypothesis. The activator plasmid DNA carrying the gene for GAL4-HAT was introduced into mouse Hepa1-6 cells together with the reporter plasmid DNA by lipofection. Significantly increased luciferase expression was observed by the co-introduction of the activator plasmid DNA. Moreover, acetylation of histone bound to the reporter plasmid DNA was enriched by the activator plasmid DNA. These results indicated that the GAL4-HAT is useful for enhanced transgene expression.

Free Research Field

遺伝子治療学