Establishment of technology to dramatically increase the expression of foreign genes introduced by viral vector

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05165
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 27040:Biofunction and bioprocess engineering-related
• Research Institution: Okayama University
• Principal Investigator: Arao Yujiro 岡山大学, 保健学域, 教授 (40151146)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 外来遺伝子発現 / ウイルスベクター / 緑色蛍光蛋白質 / 糖 / オスモライト / ERK1/2阻害剤 / ポリカチオン

Outline of Final Research Achievements

In general, the viral vector-mediated gene expression is evaluated to be relatively high. We made it possible to increase the adenoviral vector-mediated gene expresson by approximately 12-fold by culturing the transduced cells in the presence of less harmful compounds such as sugars. We also realized to increase the adeno-associated virus vector-mediated gene expression by about 40-fold by the same method. The types and concentrations of compounds that exerted the maximal increasing effect differed from cell to cell. Therefore, it was necessary to select the optimum compound for each cell. Furthermore, we show that adenovirus vector-mediated transgene expression in THP-1 cells was increased more than 500-fold by combining the enhancing effect of sugar on transgene expression with the neutralization of negative charges on the virus surface by polycations and the induction of CAR, ADV receptor, by an ERK1/2 inhibitor.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

本研究は、ウイルスベクターによる外来遺伝子発現を大幅に増やすことを可能にした。この技術は、学術的には、生物学・基礎医学研究、並びに遺伝子治療の発展に寄与すると考えられる。また、10倍発現量が増えると生産コストは10分の1に、100倍発現量が増えると生産コストは100分の1に近づくことから、社会的には、有用蛋白質の生産における生産コストを下げて適正価格による利用を実現するために貢献すると期待される。