Press Release
R&D of mRNA vaccine production technology against
covid-19 and further new coronavirus～ TMIMS and iCONM started joint research ～Summary
The Innovation Center of NanoMedicine (iCONM) and the Tokyo Metropolitan Institute ofMedical Science (TMIMS) started joint research with the aim of establishing a rapid
vaccine development technology in preparation for the re-epidemic of covid-19 and thenext coming pandemic of further new coronaviruses. An efficient procedure for theproduction of mRNA vaccine incorporated with immunostimulatory adjuvant functionality
will be optimized using iCONM’s smart nanomachine technologies and TMIMS’s expertisefor the discovery of recombinant vaccines.
June 4, 2020 – Kawasaki / Japan: The Innovation Center of NanoMedicine (President:Prof. Kazunori Kataoka, location: Kawasaki in Japan; abbreviation: iCONM) initiated acollaborative study with the Tokyo Metropolitan Institute of Medical Science (President: Dr.
Hisao Masai, location: Tokyo in Japan, abbreviation: TMIMS) on April 1st, 2020, aiming torapidly develop mRNA vaccine incorporated with immunostimulatory adjuvant functionality(Note 1) in preparation for the re-pandemic of covid-19 and the attacks by next coming
new coronaviruses. In iCONM, the Kawasaki base of “Center of Innovation Program”
granted by the Japan Science and Technology Agency (JST) of the Ministry of Education,
Culture, Sports, Science and Technology, “In-Body Hospitals” project has been proceeding
since 2013 (See: https://coins.kawasaki-net.ne.jp/en/concept/index.html). On the other
hand, TMIMS has a technology for long-term immunization using vaccinia virus and isdeveloping effective vaccines against covid-19 by applying this technology (Note 2).
Seven coronaviruses are currently known to infect humans, four of which are common coldviruses and not very serious ones. However, the outbreak of other three coronaviruses;
SARS (severe acute respiratory syndrome) in 2002, MERS (Middle East respiratorysyndrome) in 2012, and covid-19 this year, demonstrated coronavirus subspecies
occurring approximately every decade, suggesting that new coronavirus variants are likely
to occur in near future.

The aim of this collaborative study is to adapt iCONM's basic technology, mRNA loaded
smart nanomachines (Note 3), to the TMIMS’s expertise for the discovery of recombinantvaccines, and to develop a technology that can efficiently produce a vaccine in a shortperiod of time and at a low cost in preparation for the return of covid-19 and the attack offurther new coronavirus that will likely arise in the future.
(Note 1) mRNA vaccine incorporated with immunostimulatory adjuvant functionality: Inorder for mRNA vaccine to function, it is required not only to efficiently introduce mRNA
into antigen-presenting cells but also to activate them for effective antibody production.
Substances that enhance the action of vaccines in this way are called "adjuvants."
The introduction of adjuvants and mRNA into the same antigen-presenting cells enables
them to effectively induce immunity to the antigen.
S. Uchida, N. Yoshinaga, K. Yanagihara, E. Yuba, K. Kataoka, K. Itaka, "Designing
Immunoactivating Double-strand Messenger RNAs Maintaining Translation Activity throughHybridization with Poly A Sequence for Vaccination Effective" Biomaterials 150 162-170(2018) (DOI: 10.1016/j. biomaterials. 2017.09.033)(Note 2) Vaccine development using vaccinia virus: The vaccine that contributed to theelimination of smallpox is a live vaccine containing vaccinia virus classified as the same
orthopoxvirus as smallpox virus. It is often used as a basis for recombinant vaccines inrecent years due to the following reasons: the ability to be administered systemically byintravenous administration, the lack of risk of chromosomal integration withouttranslocation into the cell nucleus, the ability to infect a variety of cancer cells, and theability to transfer a wide variety of genes with a viral genome size of 200kbp. In TMIMS,
recombinant vaccines against H5N1 highly pathogenic avian influenza have beensuccessfully generated using vaccinia virus.
M. Kohara, F. Yasui, H. Kida, Y. Sakoda and K. Ishii, “Recombinant Vaccinia Virus Derived
from DIs Strains Harboring Hemagglutinin Protein Genes from New Influenza Virus”.
JP5884100B2 (2011)(Note 3) mRNA-loaded smart nanomachines: Spherical or rod-shaped molecular assembly(micelles) with a size of tens of nm formed by associating amphipathic polymers withvarious functional molecules in water. 1 nm is one billionth of a meter. If we compare theheight of a person to the diameter of the earth, the size of one cell is that of Tokyo Dome,and the size of the smart nanomachine is that of a soccer ball. Unlike DNA, mRNA serves
as a blueprint for protein synthesis outside the cell nucleus. Since it is a very unstablecompound and has a problem of causing an inflammatory reaction, it is difficult to handle
as a drug as it is, but it has been known that these problems can be solved by mounting it
on a smart nanomachine.

H. Cabral, K. Miyata, K. Osada, K. Kataoka, Block copolymer micelles in nanomedicine
applications. Chem. Rev. 118 (14) 6844-6892 (2018) (DOI: 10.1021/acs.chemrev.8b00199)
S. Uchida, K. Kataoka, Design concepts of polyplex micelles for in vivo therapeutic delivery ofplasmid DNA and messenger RNA. J. Biomed. Mater. Res. A 107 Issue 5 978-990 (2019) (DOI:10.1002/jbm.a.36614)

Innovation Center of NanoMedicine (iCONM):
The Innovation Center of NanoMedicine (iCONM) is a leading facility of King Skyfront, thatis a biotech and healthtech innovation cluster in Kawasaki City. iCONM started theoperation in April 2015 with Kawasaki Institute of Industrial Promotion in order to drive“Center of Open Innovation Network for Smart Health (COINS)” as a part of Japanese
governmental research program “Center of Innovation (COI) Stream”. Designed for the
purpose of promoting “open innovation” through industry-academia-government andmedicine-engineering collaborations with state-of-the-art facilities and experimental
equipment capable of conducting the R&D from organic synthesis and micro-processing topreclinical studies. This is a very unique research center that is hardly found in the world.
https://iconm.kawasaki-net.ne.jp/en/index.html
Tokyo Metropolitan Institute of Medical Science (TMIMS):In April 2011, three separate Tokyo research institutes were combined to form the Tokyo
Metropolitan Institute of Medicine, and the Governor of Tokyo certified our institute as apublic benefit foundation on April 1, 2012. By conducting basic and medical research
comprehensively, and translating these results into therapies, we aim to improve themedical care and contribute to the well-being of the metropolitan population.
http://www.igakuken.or.jp/english/index.html