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Special Seminar by Prof. Satoshi Uchida
Date: Jan 10, 2020

 

Development of mRNA polyplex micelles through engineering polymers and mRNA for in vivo therapeutic applications

Satoshi Uchida, Associate Professor (The University of Tokyo) 

[Abstract]

Messenger RNA (mRNA) therapeutics has demonstrated its potential in a variety of biomedical applications, including vaccinations, protein replacement therapies, and genome editing. However, mRNA has two major limitations especially for in vivo delivery: rapid enzymatic degradation in physiological environment, and strong immunogenicity. Polyplex micelles (PMs), comprised of condensed mRNA surrounded by a poly(ethylene glycol) layer, provide a promising platform to solve these issues. This platform protects mRNA from nuclease attack, and avoids mRNA recognition by innate immune receptors, simultaneously. By local injection of PMs, we succeeded in treating animal models of various diseases, including fulminant hepatitis, osteoarthritis, spinal cord injury, and intravertebral disk disease. Meanwhile, systemic injection is an easier and less invasive procedure compared to local injection, although this delivery route poses additional challenges, such as mRNA protection from nucleases for a prolonged period in blood circulation. We fine-tuned polymer structure to stabilize PMs in blood circulation, and eventually succeeded in anti-angiogenic treatment of pancreatic cancer in mice after systemic mRNA delivery. Along with polymers, we recently engineered mRNA through hybridization of functionalized RNA oligonucleotides for further improvement of in vivo PM bioavailability. These novel technologies will expand the potential of mRNA therapeutics for future clinical translation.

  Prev Special Seminar by Dr. Jiho Shin
Feb 11, 2020

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