2023 Fiscal Year Final Research Report
Research of new treatment for achondroplasia with self-amplifying RNA and lipod nano particle.
| Project/Area Number |
21K15350
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 48030:Pharmacology-related
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| Research Institution | Aichi Medical University (2022-2023)
Gifu Pharmaceutical University (2021) |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 自己増幅型RNA / 遺伝子疾患 / 核酸医薬 |
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| Outline of Final Research Achievements |
Fibrodysplasia ossificans progressiva(FOP) is one of the rare genetic disorders with soft tissue progressive ossification. It is reported to be caused by ACVR1 R206H genetic mutation, but radical treatment for this disease has not been developed. Here, we developed gene transfer method into the human cells using self-amplifying RNA(saRNA). saRNA is an mRNA which contains a target gene sequence and virus-derived RNA replicon. Since the mRNA continues to self-replicate using the virus-derived RNA replication mechanism, it can express a gene of interest for a long period of time without genome integration. Therefore, we examined whether the cell phenotype of in vitro FOP model is rescued by saRNA transfection in this research.
The FOP derived iPS significantly increased bone formation. In addition, ACVR1R206H silencing with saRNA significantly attenuated bone formation.These results showed that transfection of saRNA inhibited ACVR1R206H function and rescued abnormal bone fomation.
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| Free Research Field |
骨代謝学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題ではiPS細胞培養において、saRNAがFOPの異常な骨形成を抑えることが示された。この結果は、saRNAがFOPに対する新規治療薬の候補になる可能性を示した。
また、saRNAは核酸であるため、自由に設計が可能な物質である。そのため、手法の応用性が高く、今回ターゲットとしたFOP以外にも、軟骨無形成症など他の遺伝子疾患に対して有効なsaRNAも設計可能であると考えられる。そのため、様々な疾患への応用が考えられ、また、ゲノム編集やウイルス医薬のような危険性の高い手法を使わずに長期間の遺伝子制御が可能である点が本研究の学術的意義の高い点であると考えられる。
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