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2021 Fiscal Year Final Research Report

Cell therapy by using engineered biosynthesis of anticancer agent in tumor cells

Research Project

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Project/Area Number 19K22291
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 38:Agricultural chemistry and related fields
Research InstitutionUniversity of Shizuoka

Principal Investigator

Watanabe Kenji  静岡県立大学, 薬学部, 教授 (50360938)

Project Period (FY) 2019-06-28 – 2022-03-31
Keywords天然物 / 生合成 / 遺伝子治療 / 異種宿主発現
Outline of Final Research Achievements

One of the hurdles in practicing gene therapy is establishing a system for functional expression of heterologous genes in human cells. Here we examined whether human cancer cells could produce antibiotics when provided with a heterologous biosynthetic gene. We focused on cytochrome P450, an inherently difficult class of enzymes to produce. Specifically, we selected Fma-P450 that plays a central role in the fumagillin antimicrobial biosynthesis in Aspergillus fumigatus to examine fungal metabolite production by HeLa cells that express fma-P450 heterologously using a retroviral vector. Here we show that HeLa cells harboring fma-P450 can biosynthesize 5-hydroxyl-β-trans-bergamoten, 5-hydroxyl-β-cis-bergamoten, and cytotoxic 5-epi-demethoxyfumagillol when supplemented with the precursor β-trans-bergamotene. In conclusion, we demonstrated the feasibility of programming human cells to auto-generate antibiotics through heterologous gene introduction.

Free Research Field

天然生合成

Academic Significance and Societal Importance of the Research Achievements

本研究ではがんを対象疾患としたが、天然物の特性とアイディア次第で様々な治療戦略を立てることができる。例えば、ゲノム編集技術や組織指向性アデノ随伴ウイルスベクターを用いることで、脳や筋肉など組織選択的に天然物生合成遺伝子を送達でき、神経疾患や心疾患など対象疾患の範囲を拡大することも可能かもしれない。あるいは、植物由来天然物の生合成遺伝子も本研究にコンセプトに適用できるだろう。本法は、特殊な機器・設備を必要とせず、ウイルスベクターも市販されているため、動物細胞用の培養機器・試薬があれば容易に実施可能である。本研究のコンセプトが分野を問わず広く多くの研究者に普及し、実用化に至ることを願う。

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Published: 2023-01-30  

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