2020 Fiscal Year Final Research Report
Development of Next-Generation Gene Therapy for Heart Failure Through Synthetic Biology Approach
| Project/Area Number |
19K23988
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
0903:Organ-based internal medicine and related fields
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-08-30 – 2021-03-31
|
| Keywords | 心不全 / 遺伝子治療 / 合成遺伝子回路 / 表現型スクリーニング / microRNA / 合成生物学 |
|---|
| Outline of Final Research Achievements |
We developed an innovative gene therapy that enables cardiomyocytes to express therapeutic microRNAs with spatiotemporal precision. We performed massively parallel combinatorial phenotypic screening of microRNAs. We identified the combination of microRNAs that synergistically protect cardiomyocytes against pathological stressors. We developed synthetic gene circuits that consist of a logic gate to discriminate cell-types and pathological conditions, a closed-loop circuit that fine-tunes gene expression levels based on the intensity of pathological stress, and a drug-inducible regulation system. When we delivered synthetic gene circuits harboring therapeutic microRNAs into cardiomyocytes, protective effects against pathological stressors were observed only under intended conditions. Our next-generation gene therapy would realize precision medicine at the cellular level for the treatment of heart failure and provide more efficient and safe therapeutic platforms than current therapies.
|
| Free Research Field |
循環器内科学
|
| Academic Significance and Societal Importance of the Research Achievements |
超高齢化社会である我が国では、心不全の罹患率及び死亡率が急増しており、根本的解決につながる治療法の開発が急務である。心不全の病態は、様々な細胞や生体物質が構成する生物学的ネットワーク全体の偏移である。よって、その根本的解決には適切な因子を、適切な時期に、適切な量を、適切な細胞で発現させる必要がある。
本研究では、以上の問題点を解決する心不全の次世代遺伝子治療を開発した。この次世代遺伝子治療は細胞レベルの個別化医療を可能にし、現在の治療戦略よりも効果的かつ副作用の少ない心不全治療を提供することが期待できる。さらに、本研究は合成遺伝子回路を用いた遺伝子治療開発の標準化手法を提供する。
|
