Cutting edge Seminar

 

 

Speaker:  Yoshinobu Takakura　（Professor, Department of Biopharmaceutics and Drug Metabolism Graduate School of Pharmaceutical Sciences Kyoto University）

Title:  Exosome-based nucleic acid drug delivery system

 

Date&Time:  8 Nov. (Wed.) 2017, 12:00-13:00

Venue: Conference Room(1F), IMEG

 

Abstract:

A variety of nucleic acid drugs have been studied as promising drug candidates for the treatment of a wide range of diseases, including cancer, viral diseases and other incurable diseases. For a successful therapy with these nucleic acid drugs, it is important to establish a rational strategy for the delivery of the nucleic acid drugs. Exosome are extracellular vesicles secreted from most types of cells. As exosomes are endogenous delivery vehicles responsible for intercellular transport of biomolecules including nucleic acids, natural and genetically engineered exosomes are expected to become potent delivery systems for nucleic acid therapeutics. We have developed novel methods of labeling exosomes with luciferase and ¹²⁵I using fusion proteins to study pharmacokinetics of exogenously administered exosomes, one of the most important issues for the development of exosome-based delivery systems. Based on the findings, we recently developed a novel exosome-based antigen-adjuvant co-delivery system using genetically engineered tumor cell-derived exosomes containing endogenous tumor antigens and CpG DNA, a potent adjuvant. Vaccination with CpG DNA-modified exosomes exhibited a strong antitumor immunity, indicating that our novel exosome-based antigen-adjuvant co-delivery system can be a useful approach in cancer immunotherapy.

 

References:

1. Matsumoto, Y. Takahashi, M. Nishikawa, K. Sano, M. Morishita, C. Charoenviriyakul, H. Saji, Y. Takakura. Accelerated growth of B16BL6 tumor in mice through efficient uptake of their own exosomes by B16BL6 cells. Cancer Sci, in press, 2017
2. Morishita, Y. Takahashi, M. Nishikawa and Y. Takakura. Pharmacokinetics of Exosomes–an Important Factor for Elucidating the Biological Roles of Exosomes and for the Development of Exosome-Based Therapeutics. J Pharm Sci, in press , 2017
3. Charoenviriyakul C, Takahashi Y, Morishita M, Matsumoto A, Nishikawa M, Takakura Y. Cell type-specific and common characteristics of exosomes derived from mouse cell lines: yield, physicochemical properties, and pharmacokinetics. Eur J Pharm Sci, 96, 316-322, 2017.
4. Matsumoto A, Takahashi Y, Nishikawa M, Sano K, Morishita M, Charoenviriyakul C, Saji H, Takakura Y. Role of Phosphatidylserine-Derived Negative Surface Charges in the Recognition and Uptake of Intravenously Injected B16BL6-Derived Exosomes by Macrophages. J Pharm Sci, 106, 168-175, 2017.
5. Morishita M, Takahashi Y, Matsumoto A, Nishikawa M, Takakura Y. Exosome-based tumor antigens–adjuvant co-delivery utilizing genetically engineered tumor cell-derived exosomes with immunostimulatory CpG DNA. Biomaterials, 11, 55-65, 2016.
6. Yamashita T, Takahashi Y, Nishikawa M, Takakura Y. Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation. Eur J Pharm Biopharm, 98, 1-8, 2016.
7. Imai T, Takahashi Y, Nishikawa M, Kato K, Morishita M, Yamashita T, Matsumoto A, Charoenviriyakul C, Takakura Y. Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice. J Extracell Vesicles, 4, 26238, 2015.
8. Morishita M, Takahashi Y, Nishikawa M, Sano K, Kato K, Yamashita T, Imai T, Saji H, Takakura Y. Quantitative Analysis of Tissue Distribution of the B16BL6-Derived Exosomes Using a Streptavidin-Lactadherin Fusion Protein and Iodine-125-Labeled Biotin Derivative After Intravenous Injection in Mice. J Pharm Sci, 104, 705-713, 2015.
9. Takahashi Y, Nishikawa M, Shinotsuka H, Matsui Y, Ohara S, Imai T, Takakura Y. Visualization and in vivo tracking of the exosomes of murine melanoma B16-BL6 cells in mice after intravenous injection. J Biotechnol, 165, 77-84, 2013.

 

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