最先端研究セミナー

Abstract:

In recent years, mitochondrial dysfunction has been implicated in a variety of diseases, including neurodegenerative diseases, diabetes, cancer and a variety of inherited mitochondrial diseases. This makes this organelle a promising therapeutic drug target, and mitochondrial therapy would be expected to be useful and productive for the treatment of various diseases. To achieve such an innovative therapy, it will be necessary to deliver therapeutic agents into mitochondria in living cells. However, only a limited number of approaches are currently available for accomplishing this. We recently developed a MITO-Porter, a liposome-based carrier that can be used to introduce macromolecular cargos into mitochondria via membrane fusion. Using the green fluorescence protein as a model macromolecule and confocal laser scanning microscopy as the detection method, we were able to confirm that the MITO-Porter is, in fact, capable of delivering a macromolecule to mitochondria. To date, we have demonstrated the utility of this MITO-Porter in treating some diseases in animal models. We also showed that the mitochondrial delivery of antisense oligo-RNA by the MITO-Porter results in the knockdown of mitochondrial RNA, having a functional impact on mitochondria. In this presentation, we summarize the current state of mitochondrial drug delivery systems (DDS) focusing on our research and show some examples of regulating mitochondrial functions using mitochondrial DDS.

Reference:

1. Abe J, Yamada Y, Takeda A, Harashima H. Cardiac progenitor cells activated by mitochondrial delivery of resveratrol enhance the survival of a doxorubicin-induced cardiomyopathy mouse model via the mitochondrial activation of a damaged myocardium. J Control. Release 269: 177-188 (2018).
2. Takano Y, Munechika R, Biju VP, Harashima H, Imahori H, Yamada Y. Optical Control of Mitochondrial Reductive Reactions in Living Cells using an Electron Donor-Acceptor Linked Molecule. Nanoscale 9: 18690-18698 (2017).
3. Yamada Y, Ishikawa T, Harashima H. Validation of the use of an artificial mitochondrial reporter DNA vector containing a Cytomegalovirus promoter for mitochondrial transgene expression. Biomaterials 136: 56-66 (2017).
4. Yamada Y, Nakamura K, Abe J, Hyodo M, Haga S, Ozaki M, Harashima H. Mitochondrial delivery of Coenzyme Q₁₀ via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver. J Control Release 213: 86-95 (2015).
5. Furukawa R, Yamada Y, Kawamura E, Harashima H. Mitochondrial delivery of antisense RNA by MITO-Porter results in mitochondrial RNA knockdown, and has a functional impact on mitochondria. Biomaterials 57: 107-115 (2015).

担当分野：　薬剤情報分析学　石塚（内線：4559）

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