Kawasaki Skyfront i-Newsletter

Kawasaki Skyfront i-Newsletter

Press Releases vol.4_2

Kawasaki INnovation Gateway at SKYFRONT (KING SKYFRONT), Coastal Area International Strategy Office, Kawasaki City, Japan

For immediate release: 25 June 2015

Subject line: Fine-tuning of chemical structure of mRNA carriers for clinical application

(Kawasaki, Japan, 25 June 2015) Fine-tuning of chemical structure of mRNA carriers for clinical application is reported by researchers affiliated with Kawasaki INnovation Gateway at SKYFRONT, Japan.

Further information about science and technology projects at Kawasaki City is available in the Kawasaki SkyFront iNewsletter that highlights research being conducted by scientists and industries affiliated with Kawasaki INnovation Gateway at SKYFRONT (KING SKYFRONT)—the City’s flagship science and technology hub focused on open innovation in the life sciences and environment.

KING SKYFRONT is located on the opposite side of the Tama River that separates Tokyo International Airport (also known as Haneda Airport) and the Tonomachi district of Kawasaki. The Airport plays an important role in the globalization of the innovative activities of scholars, industrialists and City administrators based at KING SKYFRONT.

June 2015 Issue of Kawasaki SkyFront iNewsletter: http://inewsletter-king-skyfront.jp/en/

Fine-tuning of chemical structure of mRNA carriers for clinical application

Messenger RNA (mRNA) has been paid attention as a potential candidate for nucleic acids drug. However, the very labile nature of mRNA has hindered its clinical application. Polyion complex formed from mRNA and polycations, which is termed ‘Polyplex’, can protect mRNA from enzymatic degradation and enhance its cellular uptake. Fine-tuning of the chemical structure of polycations dramatically improve the ability of polyplex to deliver mRNA.

Prof. Kazunori Kataoka and co-workers at the University of Tokyo synthesized the polyaspartamides possessing the different number of aminoethylene repeats in their side chain. By applying the polyaspartamides for mRNA carriers, they found that the polyaspartamides possessing odd number of aminoethylene repeats (PA-Os) provided more persistent protein expression compared with those possessing even number repeats (PA-Es).

Prof. Kataoka and his team also revealed that, despite lower capacity of endosomal escape than PA-Es, the carriers composed of PA-Os had high stability in the cytoplasm allowing retention of mRNA stably inside the carriers. Eventually, PA-Os can provide protein expression in a long and sustained manner. These feature are in sharp contrast to the case of DNA delivery, where PA-Es exhibited high capacity due to the facilitated endosomal escape.

The researchers concluded that the sophisticated molecular design of carriers is important for realizing clinical application using nucleic acids drugs.

Reference and affiliations

  1. 1. Hirokuni Uchida,† Keiji Itaka,† Takahiro Nomoto,‡ Takehiko Ishii,‡ Tomoya Suma,∥ Masaru Ikegami,† Kanjiro Miyata,† Makoto Oba,⊥ Nobuhiro Nishiyama,# and Kazunori Kataoka*,†,‡,§. Modulated protonation of side chain aminoethylene repeats in N substituted polyaspartamides promotes mRNA transfection. The Journal of the American Chemical Society 136 (2014)

    †Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, ‡Department of Bioengineering, Graduate School of Engineering, and §Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan

    ∥Department of Chemical and Biomolecular Engineering, The University of Melbourne, Victoria 3010, Australia

    ⊥Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan

    #Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4529 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan

*corresponding author email address: kataoka@bmw.t.u-tokyo.ac.jp

Video Feature


Nobuhiko Okabe, M.D., Ph.D.


Director General
Kawasaki City Institute for Public Health

http://inewsletter-king-skyfront.jp/en/video_feature/vol_4/feature01/

Research Highlights

Fine-tuning of chemical structure of mRNA carriers for clinical application
http://inewsletter-king-skyfront.jp/en/research_highlights/vol_4research02/

A dual role for protein Cdh7 in correct cerebellum development
http://inewsletter-king-skyfront.jp/en/research_highlights/vol_4/research01/

An enhanced model for estimating pesticide toxicity using mice with humanized livers
http://inewsletter-king-skyfront.jp/en/research_highlights/vol_4research03/

Further information:

Kawasaki City, Japan, Coastal Area International Strategy Office General Planning Bureau, City of Kawasaki,1 Miyamoto-cho, Kawasaki-ku, Kawasaki-city, Kanagawa 210-8577, Japan

EMAIL:20rinkai@city.kawasaki.jp

Polyplex prepared from polycations with odd number of aminoethylene repeats showed efficient capacity of mRNA delivery. Carriers with odd number of aminoethylene repeats (PA-Os) possessed higher stability in the cytoplasm than those with even number (PA-Es), providing persistent protein expression from the mRNA.

About KING SKYFRONT

The Kawasaki INnovation Gateway (KING) SKYFRONT is the flagship science and technology innovation hub of Kawasaki City. KING SKYFRONT is a 40 hectare area located in the Tonomachi area of the Keihin Industrial Region that spans Tokyo and Kanagawa Prefecture and Tokyo International Airport (also often referred to as Haneda Airport).

 KING SKYFRONT was launched in 2013 as a base for scholars, industrialists and government administrators to work together to devise real life solutions to global issues in the life sciences and environment.

 Website

http://www.city.kawasaki.jp/en/category/132-5-0-0-0-0-0-0-0-0.html

 

KING SKYFRONT Concept Video

https://www.youtube.com/watch?v=GKh1FCPYWmI&index=2&list=PL70Lb7fKyWsjegtd4tBfXQqbRZbeNjqwt

 

Further information

 

Kawasaki City, Japan, Coastal Area International Strategy Office

General Planning Bureau, City of Kawasaki,

 

1 Miyamoto-cho, Kawasaki-ku, Kawasaki-city, Kanagawa 210-8577, Japan

EMAIL: 20rinkai@city.kawasaki.jp

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