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

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With a view to improving gene therapy, Kazunori Kataoka at the University of Tokyo and collaborators, including researchers affliated with the Kawasaki INnovation Gateway at SKYFRONT (KING SKYFRONT), have completed a study to determine the best design of polycation structure for delivering mRNA. The researchers concluded that the sophisticated molecular design of carriers is important for realizing clinical application using nucleic acids drugs.

Polyplex prepared from polycations with odd number of aminoethylene repeats showed efficient capacity of mRNA delivery.

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

Press Release
Source: Kawasaki INnovation Gateway at SKYFRONT

For immediate release: 25 June 2015

(Kawasaki, Japan, 25 June 2015) With a view to improving gene therapy, Kazunori Kataoka at the University of Tokyo and collaborators, including researchers affliated with the Kawasaki INnovation Gateway at SKYFRONT (KING SKYFRONT), have completed a study to determine the best design of polycation structure for delivering mRNA. The researchers concluded that the sophisticated molecular design of carriers is important for realizing clinical application using nucleic acids drugs.

The findings are published in The Journal of the American Chemical Society 136 (2014)

This research is being conducted in collaboration with the Kawasaki INnovation Gateway at SKYFRONT (KING SKYFRONT), the flagship science and technology innovation hub of Kawasaki City located in the Tonomachi area of the Keihin Industrial Region that spans Tokyo and Kanagawa Prefecture and Tokyo International 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.

More information about Kawasaki INnovation Gateway at SKYFRONT: http://inewsletter-king-skyfront.jp/en/about

There is much interest in messenger RNA (mRNA) as a potential candidate for nucleic acids drug. However, the very labile nature of mRNA has hindered its clinical applications. 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.    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 American Chemical Society 136 (35), pp 12396–12405 (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(at)bmw.t.u-tokyo.ac.jp

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About KING SKYFRONT

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.

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.

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(at)city.kawasaki.jp

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Naoko Sato
Kawasaki City, Japan, Coastal Area International Strategy Office
+81 442003634
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