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From KING SKYFRONT to the world - NanoMedical Innovation

December
2018

Fascinating! Worldʼs firstmRNA therapeutics
Contents
2

6

Talking about Theme 3

Combining mRNA and DDS,
Aim for Treatment of Intractable Disease

Keiji ITAKA, Takao INOUE, Shiro AKINAGA

Research Highlights

Development of a Neuroprotective Drug Based onmRNA Medicine

Focus on development of a clinically applicable drug for treating ischemic CNS diseases

Yuta FUKUSIMA

Regulation of Gene Expression Involved in Tissue
Formation : from Basic Research to Therapeutic
Application
Shinsuke OHBALight to Cancer Immunotherapy!
Development of basic technology of cancer vaccine
using a new formation of mRNA medicine
Satoshi UCHIDA

12 Listen to COINS’ Members

What we treasure now

Miki MASAI, Daniel Gonzalez Carter, Takuya ISHII, Samuel Crowley

14 Activity Report

・10th General Meetiong
・Topics
・Challenge Cloud Funding
・COINS Seminar Report  Pick up!
・Editor’s note6Vol.

Talking about
Theme 3

Combining mRNA and DDS,
Aim for Treatment of Particular Disease
Expectations are growing for mRNA drugs that deliver messenger RNA (mRNA) to target cells andexpress necessary proteins there.We asked Dr. Keiji Itaka, Professor, Institute of Biomaterials andBioengineering, Tokyo Medical and Dental University and Dr. Shiro Akinaga, Chairman of the Board,
CEO, AccuRna, Inc., who advance R&D of mRNA medicine in COINS Theme 3 and Dr. Takao Inoue,
Head of laboratory, Laboratory of Oligonucleotide Therapeutics, Division of Molecular and Gene
Therapy Products, National Institute of Health Sciences who supports those research and developmentfrom the side of regular science, about the current situation and goals of R & D.

Takao INOUE

Keiji ITAKA

Shiro AKINAGAHead of laboratory, Laboratory of Oligonucleotide
Therapeutics
Division of Molecular target and gene therapy Products
National Institute of Health Sciences

Professor, Dept. Biofunction Research,Institute of Biomaterials and Bioengineering,Tokyo Medical and Dental University

President and CEO, AccuRna, Inc.

Dr. Inoue graduated from Faculty of Pharmaceutical
Sciences, The University of Tokyo in 1998 andcompleted Doctoral Course in Graduate Schoolof Pharmaceutical Sciences, The University ofTokyo in 2003 (PhD). He worked as AssistantProfessor at Graduate School of Pharmaceutical
Sciences, The University of Tokyo from April,2003 and was transferred to work at National
Institute of Health Sciences in October 2011.
Laboratory of Oligonucleotide Therapeutics was
newly established at National Institute of Health
Sciences in October 2013 and he was appointed
as Head of Laboratory. In April 2015, he wasseconded to AMED, responsible for allocating
budget for regular science research (Section
Chief of Office of Regulatory Science and ClinicalResearch Support). He returned to current positionin June 2017. His areas of expertise are molecularbiology, biochemistry and genetics.

Keiji Itaka, M.D., Ph.D. is a professor of Dept.
Biofunction Research, Institute of Biomaterials
and Bioengineering, Tokyo Medical and Dental
University. He graduated Dept. Of Medicine,
The University of Tokyo in 1991, worked as an
orthopedic surgeon. He started researches of
DDS, gene therapy, biomaterials, and regenerative
medicine with Prof. Kataoka in 19 9 9, a nd
got Ph. D. in 2 0 0 3 . Now he is focusing on
development of mRNA medicine, some of whichwere awarded as Best Abstract Award in mRNA
Health Conference in 2015 and 2016 and as
Mizushima Award in the Japan Society of Drug
Delivery System in 2016. He also participated in
the launch of a new venture company, AccuRna
Inc., in 2016.

Dr. Akinaga joined Kyowa Hakko Kogyo Co., Ltd,
where he engaged in exploration and evaluationof anti-cancer drugs at pharmaceutical research
center for 20 years and worked on many anticancer drug candidates. After that, he transferred
to clinical development of anti-cancer drugs andwas involved in the global development of many
drugs, anti CCR4 antibody Mogamulizumab. wasapproved for marketing in Japan in 2012 based on
the collaboration research with Professor Ryuzo
Ueda, then professor at Nagoya City University.
He became an international clinical development
director in 2006. After the establishment of Kyowa
Hakko Kirin Co., Ltd. in October 2008, he was aclinical development director of oncology group,
Executive officer of global clinical developmentin 2011, fellow in 2013.He assumed the post of
Board member at AccuRna Inc. in March 2017
and CEO in November 2018.

2 | NanoSky VOL.06 DECEMBER 2018

mRNA can be synthesized
artificially. If it is put into
practical use, a paradigm shift
will occur in personalized
treatment

stitute in creating innovative drugs as a national organization.

■ Explain the advantages of using mRNA as
medicine. What is the current status of theresearch?

■ Please introduce your research first.

Itaka: In the treatment using mRNA , we administer
mRNA encoding therapeutic proteins that can act as a
Itaka: I am originally a clinical orthopedist. When I
key molecule for treating diseases. The advantages ofwas working in a hospital, I also wished to engage inmRNA are being synthesized relatively easily and besomething new that might contribute to the future.
ing adaptable to personalized medicine by flexibly
Then, I knew a theme of DDS (Drug Delivery System),changing its sequence (Fig. 2). I think mRNA medicine
which appeared interesting and promising, and started
has the potential to cause a paradigm shift in treatthe research career on the theme. I engaged in rement. On the other hand, diseases involving various
search of regenerative medicine using DDS in the orfactors in a complex manner such as cancer, are diffithopedic field, and I have been focusing on development
cult to treat with mRNA medicine alone. In cancer,
of mRNA medicine in recent years (Figs. 1 and 2).
mRNA should be co-administered with other therapeuAkinaga: I joined Kyowa Hakko Kogyo Co. Ltd. (in thattic agents, such as anticancer drugs.
time), engaged in research of low molecular anticancer
Akinaga: mRNA medicine is roughly classified into
drugs as the senior researcher, and was promoted tovaccines and therapeutic agents. Clinical trials of thethe development position. In 2017, I retired from thevaccines are underway mainly by Western venture
former company and joined AccuRna Inc., where I
companies and some have reached phase II trials inhave been the CEO since November 2018. Currently, I
the cancer and infectious disease fields. In addition, Asengage in drug discovery research using mRNA with
traZeneca is conducting a phase II clinical trial in ischDr. Itaka and other members, along with nucleic acidemic heart diseases. Since there are many other treatmedicine research into siRNA and ASO (Fig. 1).
ments for ischemic heart diseases, the meaning of theInoue: I joined the laboratory of The University of Touse of mRNA may be controversial.
kyo just at the time when RNA interference (RNAi)
Itaka: In either case, the research is still in the prewas discovered in nematodes, and I engaged in basic
dawn stage, but the market will likely expand in the
research utilizing RNAi. Since I joined the National Infuture. Because this is a novel treatment,
stitute of Health Sciences, I have engaged in regulatory
we believe that clinical application will be accelerated
science research to study how to evaluate/assess theby targeting diseases that currently do not have treatquality and safety of nucleic acid medicines, such as
mentsiRNA and antisense, in order to put them into practiInoue: Mentioning oligonucleotide therapeutics in concal use. I also keep in mind the initiative role of our intrast to mRNA therapeutics, oligonucleotide therapeutics to remove the causative
Figure 1
molecule for the disease is being studied well as of now. In
Functions of mRNA (messenger RNA) medicine and nucleic acid medicine
2018, for example, the antiMechanism of gene expression in the cell
sense drug inotersen (trade
Cell
name: Tegsedi) and the siRTranscription
Translation
NA dr ug pat isira n (t rade
mRNA
Protein
name: Onpattro) were ap Nucleus
proved for inherited atypicalGenetransthyretin amyloidosis,*1（DNA）
an inherited neurological disease with little or no theramRNA medicine
Nucleic acid medicine
pies for them. Both oligonucleExogenous mRNA is administered
Short oligo nucleotide (e.g., siRNA and antisense) is
so that the therapeutic protein is
introduced to act on the RNA so that the protein causing
otide therapeutics degrade
newly produced.
disease is eliminated or functional protein is produced.
mRNA of the mutant transCell
Cell
thyretin that forms amyloid
Transcription
Translation
mRNA Translation
aggregation in the blood. Such
ProteinProteindrugs have set off developNucleus
Nucleusment and approval of oligonumRNA
Gene
Gene
cleotide therapeutics in Japan
（DNA）
（DNA）
and foreign countries. I feelthat the basis to facilitate

NanoSky VOL.06 DECEMBER 2018

|3

TALK
practical use of mRNA medicine is being formed.
Itaka: Nucleic acid medicine and mRNA are inseparable like both wheels of a car.+ While treatment with
antisense nucleic acid medicine reduces the expressionof the endogenous gene in the cells, mRNA medicine
produces proteins that are encoded by the mRNA.
Inoue: Since both mRNA therapeutics and oligonucleotide therapeutics are designed on the basis of thegene sequence, candidate compounds for them can be obtained
overwhelmingly more quickly
than low molecule drugs or antibody drugs, and multiple drug
combinations will be easier in the
future. They have clear principles
to control gene expression at the
RNA level and have high efficacy.
They are also appealing in thatthey harm no genes compared togene therapy or genomic gene editing.
Itaka: An article has already reported that mRNA
medicine and nucleic acid medicine were both introduced in one single cell at the same time to enhance
the therapeutic effect. Our group once had an idea tointroduce a mixture of mRNA and siRNA in a nanomachine. However, the more complex the system, themore factors produce unexpected results to make it difficult to obtain approval.
Akinaga: Even if an idea for combining mRNA therapeutics and oligonucleotide therapeutics occurs, that
seems difficult to be put into practice. That may be difficult to try.
Inoue: If a number of mRNA therapeutics or oligonucleotide therapeutics are approved, and expertise inquality control or safety evaluations are accumulated in
the future, the combination of them will be popularized. I think regulations would be less strict for combinations of drugs similarly constituted by nucleic acids
than those for combinations of drugs with completely
different structures. The accumulation of experience inreviews and risk-benefit viewpoints are the keys, andat least the combinations of more than one mRNA
therapeutics or more than one oligonucleotide therapeutics could be accepted in the future. Because it is clearthat combinations of expression controls by mRNA or
oligonucleotide greatly expand the therapeutic options,
I have expectations of future progress in combination
therapy.

DDS is used to deliver mRNAto cells in a stable form
■ Why is it necessary to combine with DDS?

Itaka: Since mRNA is very unstable in vivo, it is difficult to deliver to mRNA. Although RNA may be designed to function in the cell more easily, the priority is
to deliver mRNA securely. For example, while studies
on DDS of low molecular drugs focus on retention andstability in the blood, in DDS of mRNA, it is uncertain
whether an increase in the amount of mRNA reaching
the target simply improves the therapeutic effect. On
the other hand, DDS is definitely essential, and the useof PEGylated carrier is effective for better protein expression even in local administration.
Akinaga: We think DDS should be used ingeniously inthe combination of mRNA therapeutics and oligonucleotide therapeutics mentioned before. Combinations ofmRNA and oligonucleotide could result in better effects
than the separate use of them.
Itaka: In the future, the ideal formulation will be carrying more than one nucleic acid medicine or mRNA together in a nanomachine to achieve a better effect. As
a strategy to take advantage of the properties ofmRNA, we consider the direction to keep the target
cells alive or enhance their functions to be more important, rather than the purpose of killing the target cells
as like cancer treatment.
Akinaga: One of our social missions is to develop adrug with strong unmet needs and great meaning,such as that for a rare disease caused by an abnormality in a specific gene, rather than disFigure 2
eases with various therapies like cancers.
Characteristics and problems of mRNA medicine
Itaka: Use of DDS is already an esmRNA expresses protein in the cytoplasma.
tablished concept now, and the reIt can be used in any cells in principle (e.g., nerve and cartilage).
search field of DDS has matured in apositive sense. In the current phase,mRNA has no risk of being inserted in the host genome.
we have to use currently available
It can be used without the risk of oncogenesis.
DDS securely and select what to set
in while improving DDS methods. AlmRNA is very unstable in vivo.
A DDS is needed to hold mRNA stably and deliver it to the target cells.
though DDS is basically used for systemic administration, mRNA should
mRNA induces immune responses
first be administered locally andA mechanism for regulating immunogenicity is needed
eventually move to the next step of(mRNA modiﬁcation and DDS).
systemic administration, considering
the risk of manipulating the gene,

4 | NanoSky VOL.06 DECEMBER 2018

which is contrary to low molecular drugs.

■ Let u s know t h e issu es in resea rc h a n ddevelopment of mRNA therapeutics and future
resolutions
Inoue: I would like more researchers to study mRNA
therapeutics. The Society of DDS covers only a few
topics of mRNA.
Itaka: I fully understand that mRNA is difficult to obtain substance patents by itself, and many hesitate tocommercialize it. That is why it is necessary to combine DDS to patent it. I’d like to accumulate evidenceof its efficacy first through actual use in patients, even
if only slightly.
Akinaga: AccuRna owns the patents for DDS nano-micelles that were inherited from Dr. Kazunori Kataoka.
So, we’d like to select mRNA to be inserted through discussions with Dr.
Itaka and start a clinical trial in twoor three years as a goal, while paying
attention to research in the improvement of nano-micelles at the sametime. Indeed, I’d like to say conservatively that we will start clinical trials
in five years but that would be taken
to be lack of motivation, while starting
within a year is unrealistic. So, I say
that the goal may be two or three
years. If I were a CEO of an American company, I’d bedismissed with such a sense of speed (laugh).
Itaka: No mRNA medicine has been used clinically yet.
Although the first-mover does exist, the winner takes
all attitudes are not applicable in the medical sector,
contrary to the IT community. We’d like to proceedwith the development consulting with the regulatory
authorities about specific indications for mRNA medicine.
Inoue: Consultation should be held as early as possiblereferencing the regulation for previous items developed.
Akinaga: Japan has already been fallen behind West-ern countries in the development of mRNA vaccines.
Foreign venture companies are operating well-designed
mRNA businesses. If this situation remains unchanged,
Japan will not be able to manufacture mRNA vaccines
but will have to import them.
Itaka: The members of today’s three-way conversation
are a researcher, a person in chargeof regulatory science, and the CEO of
a venture company, symbolizing thecurrent stage of mRNA medicine development. We have all reached thepoint of no return at respective standpoints (laugh). It is important to haverealistic concepts premising actual
progress toward clinical phase, instead of remaining in non-clinicalphase to obtain results from animal
experiments.
Inoue: The approval of oligonucleotide therapeutics has
prepared the way from the research and development
to clinical application. It is important to discuss how to
respond to personalized medicine from now on.
Akinaga: Although looking for and responding to various unmet needs are important; I will first proceedwith development to obtain approval selecting a disease
more suitable for mRNA.
Inoue: If mRNA therapeutics is recognized more in
the future, pharmaceutical companies and researchers
will enter this field in Japan as well. To take the initiative, I will proceed with preparation of the regulations
as soon as possible and facilitate the developmentsfrom the view of public communication such as holding
symposiums.
(Facilitator: Ayumi Kojima, science writer)

Terminology＊1 Hereditary atypical transthyretin amyloidosis
A type of amyloidosis where a protein amyloid is deposited in systemicorgans to cause various symptoms. In atypical transthyretin amyloidosis, anamyloid precursor protein with one amino acid mutated is produced mainlyin the liver and deposited systemically. The disease is treated by livertransplantation.

NanoSky VOL.06 DECEMBER 2018|5

Reserch
Highlights

1

Theme 3Development of a Neuroprotective Drug
Based on mRNA Medicine

Focus on development of a clinically applicable drug for treating ischemic CNS diseases
Ischemic CNS disease suddenly deprives the body of the function to control body movements, and the lost
function is never recovered. Although development of a neuroprotective drug and neuro-regenerative medicine
for ischemic damage may be an ardent wish of humans, there are a number of obstacles in the development ofdrugs targeting the CNS. We have demonstrated the neuroprotective effect of messenger RNA (mRNA) medicine
using polymer micelles against ischemic neuronal death. Believing that mRNA medicine may overcome the
CNS-specific challenges, we are working on the further development of therapies.

Yuta FUKUSHIMA
Assistant professor,
Department of Biofunction Research,Institute of Biomaterials and Bioengineering,Tokyo Medical and Dental University

Ischemic CNS diseases, such as cerebral infarction,
are mainly characterized by their sudden onset in any
person, as well as their neurological sequelae lasting fora lifetime once established. Major therapies that havebeen shown to have efficacy in cerebral infarction are
only hyperacute recanalization therapy ＊1 andrehabilitation in the early phase of onset. Unfortunately,
none of therapies that humans have long sought, suchas drugs to protect neurons ＊2 from cell death andregenerative medicine for established sequela, haveachieved clinical application at present. Although not afew substances were expected to have neuroprotective
effects against ischemic CNS diseases, they all had
unsuccessful results in clinical trials due to huge
obstacles, such as CNS-specific problems in drugdelivery and adverse reactions. Hence, our researchgroup focused on the mRNA medicine using polymer
micelles (Fig. 1) that locally produces high protein
expression, and we conducted a therapeutic research toverify the neuroprotective effect of the mRNA expressing
brain-derived neurotropic factor (BDNF).＊3 BDNF is a
protein abundant in brains with physiologicalneuroprotective effects. While it is secreted not only
from the neurons but from the glial cells,＊4 particularly
in ischemic conditions, local decreases in its expression
are also known to be involved in the vulnerability ofneurons against ischemia. Although protein drugs were
expected as neuroprotective drugs, excessive
administration was needed to deliver them from theperipheral blood or cerebrospinal fluid (CSF) to thelesion, posing a problem of adverse reactions. This
research used the rat global ischemia model that
produces transient severe ischemic damage. Particularly

6 | NanoSky VOL.06 DECEMBER 2018

in the hippocampus, ＊5 only the neurons in the CA1
region slowly result in cell death after a grace period of
about two days from the ischemia, which is acharacteristic cell death process called delayed neural
death. As the route for local expression of mRNA in the
hippocampus, we adopted administration in the ventricle
near the hippocampus, which is filled with CSF.
Administration of BDNF-expressing mRNA using
polymer micelles via this route of administration
obtained continuous BDNF expression in the
hippocampus for two to four days. As a result, theneuroprotective effect against delayed neural death in
the hippocampal CA1 was confirmed in the
immunohistochemical-stained rat hippocampal slices.
Furthermore, a behavioral test reflecting short-term
memory indicated its efficacy as well (Fig. 2). This
therapeutic experiment also obtained an interesting
result that BDNF was majorly expressed in theastrocytes＊6 that compose the largest proportion in the
CNS.
This result demonstrated that the therapy to locally
express the BDNF-expressing mRNA in the ischemic
brain lesion using polymer micelles is promising as
neuroprotective therapy, which was difficult to develop
due to the CNS-specific problems in drug delivery andadverse reactions. The following characteristics ofmRNA medicine delivered via polymer micelles are
suitable for ischemic CNS diseases: 1) transient gene
expression, 2) no serious adverse reactions because it is
not incorporated in the host genome, and 3) no need fora promoter that allows unlimited cell species forexpression. We would like to apply it to regenerative
medicine research as well.

Figure 1. A nanomachine enclosing mRNA medicine

Block copolymer

Polymer nano-micelle
Stably retains mRNA inside the carrier

Poly-amino acid

PEG

In vivo transportation of mRNA
The surface covered with PEG
Avoids recognition of mRNAby the Toll-like receptors

mRNA
O

H
N
O
HN

Poly(Aspertic acid)-Diethylene triamineP(Asp(DET))
NH2

N
H

NH2

Exemplary structure of poly-amine acid
= P[Asp(DET)]

50-70 nm

Controls immunogenicity of mRNA

When block copolymer synthesized from polyethylene
glycol (PEG) and poly-cation is mixed with mRNA, they are
self-assembled to from polymer micelle with the surface
covered with PGE that contains mRNA aggregated in its
central portion.

Figure 2. Neuroprotective effect of BDNF mRNA against delayed neural deathControl

Ischemia
untreated

Ischemiatreated with
BDNF-mRNA

Cell count of living neurons(%control)a. Neuroprotective eﬀect against delayed neural death in rat hippocampal slice
110
100
90
80
70
60
50
40
30
20
10
0

Control Ischemia Ischemia
untreated treated with
BDNF-mRNAb. Improvement in short-term memory in behavioral evaluation using Y maze

Normal behavior (%)

80
75
70
65
60
55
50

Control Ischemia Ischemia
untreated treated with
BDNF-mRNA

Terminology＊1 Hyperacute recanalization therapy
A therapy to recanalize the artery occluded with emboli. It is used in limited cases withinseveral hours after onset. Two modalities are indicated for this treatment: intravenous
administration of thrombolytic agents and endovascular treatment with thrombus retrieval
devices.
＊2 Neurons
Neurons serve as the entity of information processing, the primary function of the nervous
system through intracellular conduction of membrane potential and intercellular chemicaltransmission. Neuronal death causes disorders in various neurologic diseases.
＊3 Brain-derived neurotropic factor (BDNF)
A neurotrophic factor protein that regulates various physiological functions, such as learningand development. BDNF is expected to be used as medicine because it is deeply involvedin maintenance of neural survival. However, it has not been applied clinically due to various
obstacles to its delivery to the CNS in a form of protein drug.

＊4 Glial cells
A collective term referring to the cells constituting the nervous system other than theneurons. Although they were considered to be glue cells that merely sustain the neuron in
the past, now they have been revealed to have various functions.
＊5 Hippocampus
A region in the brain involved in memory and space perceptional function. Because thehippocampus is very vulnerable against ischemic damage, it has had a number of findings
accumulated as a target of studies on ischemic neuronal death.
＊6 Astrocytes
A type of glial cells that accounts for the majority in the CNS. Its various functions gather
great scientific interest.

NanoSky VOL.06 DECEMBER 2018|7

Reserch
Highlights

2

Theme 3

Regulation of Gene Expression Involved
in Tissue Formation: from Basic Researchto Therapeutic Application
Understanding the mechanism of gene expression＊1 involved in cell formation seems to be the key toregeneration or repair of the tissue. In recent years, the regulatory mechanism of gene expression bytranscription factors＊2 important in the formation or maintenance of the tissues is being clarified in genomewide manners. In the therapeutic application of such basic knowledge, a strategy to intracellularly expressmRNA of “therapeutic transcription factors” that regulate expression of genes effective for treatment seems
to be promising. I proceed with the study to identify the mechanism of gene expression that can be fed backtherapeutically and to contribute to the development of therapy for musculoskeletal disorders.

Shinsuke OHBA
Associate Professor, Laboratory of Clinical
Biotechnology, Center for Disease Biology
and Integrative Medicine, Graduate School of
Medicine, The University of Tokyo

Mammalian skeletons are generated by chondrocytesthat form the cartilage and osteoblasts that form thebone. Cartilage formed during the fetal stage regulates
skeletal growth until puberty and plays important roles
in locomotion all our lives.
In tissue formation, the transcription factors should
function normally to correctly express the genes involved in formation/maintenance of the cells constituting the tissue. Understanding such mechanisms is theshortest way to develop tissue regenerative/repairing
therapy.
We have been working on the identification of theregulatory mechanism of gene expression important for
cartilage/bone formation using mouse genetics or molecular biological approaches. As a result, we discoveredthat the transcription factor RUNX1＊3 is expressed in
the adult articular cartilage and induces expression of
the gene of type II collagen, which is a major component of the cartilage. Furthermore, RUNX1 expression
disappeared in patients with osteoarthritis, where functions of joints as cushion and hinge are affected due todegeneration of the articular cartilage (Reference 1). We
are currently aiming to identify the regulatory mechanism of gene expression in chondrocytes and osteoblasts
by taking advantage of genome-wide analyses using
next-generation sequencers. We have identified themodes of actions of transcription factors SOX9＊4 andSP7＊5 in the whole genome and obtained genome-wide
evidence of their importance in skeletal formation (References 2 to 4).
The above basic findings suggest that intracellular
expression of therapeutically effective transcription fac-

8 | NanoSky VOL.06 DECEMBER 2018

tors (therapeutic transcription factors) leads to direct
and efficient therapies. In gene expression, the a specificportion of genomic DNA encoding genetic informationof a protein is copied as messenger RNA (mRNA) andfunctions as the blueprint for synthesis of the protein.
Application of mRNA is therefore expected as a new
nucleic acid medicine. Hence, in cooperation with Professor Keiji Itaka, Professor Kazunori Kataoka, and coworkers, I examined whether delivery of the therapeutic transcription factor RUNX1 into the joint via
nanomachine can prevent cartilage degeneration andsuppress the progression of osteoarthritis. Polymer micelles encapsulating RUNX1 mRNA were administeredinto the knee joint of osteoarthritis model mice once every three days for a month. Progression of osteoarthritis
was suppressed in the articular cartilage of the RUNX1mRNA group compared to the control mRNA group(Fig. 1: Reference 5), accompanied with enhanced expressions of type II collagen, which is a major cartilage
matrix protein, transcription factor SOX9, which is essential for cartilage formation and proliferating cell nuclear antigen (PCNA), which is a marker of cell proliferation (Reference 5).
As described above, we are developing the platform,
where the mechanism of gene expression involved in
the formation and maintenance of the tissue is identified, and the basic findings are applied to treatment via
mRNA delivery with nanomachines. I will continue
working on identification of mechanism of gene expression and therapeutic transcription factors that can be
fed back to treatment to contribute to the developmentof therapies for musculoskeletal disorders.

Figure 1

Control group

RUNX1 mRNA group

The control group shows surface curing-up, degeneration and abrasion (yellow arrows) of thearticular cartilage (stained red) , which are suppressed in the RUNX1 mRNA group. Magniﬁed
images of the rectangular parts are shown in the bottom of respective panels.

Terminology＊1 Gene expression
Gene expression refers to protein synthesis based on genetic information. It isroughly divided into transcription (synthesis of mRNA through the actions oftranscription factor and basic transcription machinery) and translation (protein
synthesis based on genetic code copied in mRNA).
＊2 Transcription factor
A factor that recognizes and binds to a specific DNA sequence to regulate thetranscription process of genetic information on the DNA to mRNA.
＊3 RUNX1 (runt-related transcription factor 1)
A transcription factor encoded by RUNX1 gene that belongs to RUNX gene family.
RUNX1 is known to be involved in cartilage formation and act as the transcription
factor essential for hematopoiesis.
＊4 SOX9
SOX9 is one of the SRY-related HMG-box (Sox) family proteins and acts as
a transcription factor. Proteins with highly conserved HMG box is collectively
called the Sox family.SOX9 has important roles in skeletal formation as well as
development of the gonads, hair follicles, nerves, heart, pancreas, intestines, andinner ears.

References
1. Yano F, Hojo H, Ohba S, Fukai A, Hosaka Y, Ikeda T, Saito T, Hirata M,
Chikuda H, Takato T, Kawaguchi H, Chung UI: A novel disease-modifying
osteoarthritis drug candidate targeting Runx1. Annals of the Rheumatic
Diseases 72(5):748-753, 2013
2. Ohba S, He X, Hojo H, McMahon AP: Distinct transcriptional programs underlie
Sox9 regulation of the mammalian chondrocyte. Cell Reports 12(2):229-243,
2015
3. Hojo H, Ohba S, He X, Lai LP, McMahon AP: Sp7/Osterix is restricted
to bone-forming vertebrates where it acts as a Dlx co-factor in osteoblast
specification. Developmental Cell 37(3):238-253, 2016
4. Hojo H, McMahon AP, Ohba S: An emerging regulatory landscape for skeletal
development. Trends in Genetics 32(12):774-787, 2016
5. Aini H, Itaka K, Fujisawa A, Uchida H, Uchida S, Fukushima S, Kataoka K,
Saito T, Chung UI, Ohba S: Messenger RNA delivery of a cartilage-anabolictranscription factor as a disease-modifying strategy for osteoarthritis treatment.
Scientific Reports 6:18743, 2016

＊5 SP7
A transcription factor that belongs to the SP family. SP7 is strongly expressed in
the osteoblasts and their precursors. SP7 knockout mice have no bone developed
systemically.

NanoSky VOL.06 DECEMBER 2018|9

Reserch
Highlights

3

Theme 3

Light to Cancer Immunotherapy!
Development of basic technology ofcancer vaccine using a new formationof mRNA medicine＊1

As exemplified by the Nobel Award to Dr. Tasuku Honjo, cancer immune therapy is gathering attention inrecent years, although the therapy is effective in only a few patients. More patients could obtain benefits from
immune therapy by concurrent use of a cancer vaccine with the existing immune therapy. Now we havesuccessfully developed the basic technology for a cancer vaccine using a novel nucleic acid medicine RNA.

Satoshi UCHIDA
Project Assistant Professor,
Department of Bioengineering,
Graduate School of Engineering,
The University of Tokyo

Cancer immune therapy removes the cancer cellswith the patient’s own immunity. It is characterized by
the long-lasting effect capable of controlling relapse ofcancer, contrary to the existing surgical therapy, chemotherapy, and radiotherapy. It is gathering attention
also because of the Nobel Award to Dr. Honjo for thedevelopment of the drug to activate immunity against
cancer in 2018. However, this drug is effective in only afew patients. On the other hand, animal experiments
and clinical studies have revealed that more patientscan benefit from immune therapy through concurrent
use of a cancer vaccine to induce immunity against theproteins that exist only in the cancer cells (caner antigens).＊2
Conventional vaccines obtain immunity against pathogens by administering proteins derived from the pathogens in advance. A cancer vaccine obtains immunity to
attack cancer cells by administering cancer antigens inadvance. Cancer vaccines corresponding to individual
patients should be manufactured rapidly here because
cancer antigens differ by patient, contrary to pathogenic
antigens. For such personalized treatments, a method toadminister to patients messenger RNA (mRNA), a novel
nucleic acid medicine designed to have the cancer antigen be produced in the patient’s body, allowing production of a cancer vaccine rapidly at low cost (Fig. 1). In
this research, we developed the basic technology to enhance the effect of this mRNA vaccine.
For effective action of the vaccine, in vivo productionof cancer antigens is necessary as well as concurrent

10 | NanoSky VOL.06 DECEMBER 2018

immune activation. Thus, an immunostimulator＊3 is administered in combination with the vaccine (Fig. 1).
However, there have been problems that this immunostimulator weakens the activity of mRNA, that it exerts
no effect because of its in vivo distribution at a site different from that of the mRNA, and that it induces adverse reactions. For these problems, we developed immuno-stimulating mRNA where mRNA has its own
immuno-stimulating effect. In specific, when mRNA isbound to its counterpart RNA (complementary RNA),＊4 adouble strand RNA structure is formed by a pair of
RNA chains, which activates the immunity (Fig. 2). The
mRNA simultaneously produces the cancer antigen. In
this study, we optimized the design from the various
double strand structures and improved the vaccination
effect in animal experiments. Its effect was also demonstrated in an experiment in human cells. In this method,
the mRNA action is conserved, and the mRNA and theimmunostimulator will not be distributed in different
sites. Furthermore, this vaccine is decomposed in several days after the administration, posing no concerns
about adverse reactions.
From now on, I will study whether the mRNA developed in the present research actually has a suppressive
effect on cancer growth in animal studies and seek its
clinical application by using concurrently with the drug
developed by Dr. Honjo. I will work on the research to
make my dream of developing drugs useful for patientscome true.

Figure 1. mRNA vaccine against cancer

A dendritic cell withits mRNA activated

The T cells recognize thecancer antigen on the cancer
cells and damage them.

The dendritic cell partiallypresents the cancer antigen

CancerantigenmRNA

A lymphocyte
targeted to cancer (T cell)

Immunostimulator
Dendritic cell
Immunostimulator activatesthe dendritic cells

Activated dendritic cell
The T cell has the antigen presented,
is activated and then proliferates.

Cancer cells*Dendritic cell … Exists in the skin, airway, and intestines that contact the outer environment. This cell takes up foreign matter andpresents the antigen to the lymphocytes* T cells ………… A type of lymphocytes that attacks the cancer cells and cells infected with the pathogen and regulates the functions ofother immune cells.

Figure 2. Design of a double strand mRNA and vaccine effectmRNA

Poly AW hen the whole leng th of m R N A was bound to its
complementary RNA, immunostimulation was obtained fromthe double strand RNA structure, although production of theantigen protein from the mRNA was lost.

W h e n th e c o m ple m e nta r y R N A was b o u n d o nly tot h e se q u e n c e c alle d p oly A at th e e n d of m R N A ,immunostimulation was obtained while production of theantigen protein from the mRNA was maintained as well,and this design was therefore adopted.

Proliferation of the dendritic cells in the lymph nodeSingle strand mRNA Double strand mRNA

(Top): mRNA was administered to mouse lymph node and the activated dendritic cells
were stained red 24 hours after. The blue portion indicates the nucleus. Proliferationof the activated dendritic cells was noted in the double strand mRNA group.
(Right): An mRNA to develop a model antigen was administered to the mouse lymph
node and the number of cells reacting to the antigen was counted seven days after.
The number of cells increased in the double strand mRNA group with increasing
vaccine eﬀect conﬁrmed.

The number of immune cells
reacting to the antigen

Not administered

400

Vaccine eﬀect

300

200

100

0

Not
Singleadministered strandmRNA

DoublestrandmRNA

Terminology＊1 Cancer vaccine
A drug to be used in the therapy where a cancer antigen is administered toinduce immunity against the antigen and attack the cancer cells.
＊2 Cancer antigen
A substance that does not exist in normal cells but in cancer cells and serves asa marker for the immune cells to attack the cancer cells.
＊3 Immunostimulator
A substance to enhance the vaccine effect by inducing an inflammatory reactionin the vaccine administration site. It is also referred to as an adjuvant. Aluminum
salts are currently used as immunostimulators.

＊4 Complementary RNA
RNA consists of four bases: adenine (A), guanine (G), cytosine (C), and uracil (U).
A and U mutually bind and G and C mutually binds each other as well. An RNA
chain consisting of bases that mutually bind to the bases of another RNA chain iscalled complementally RNA.

References
S. Uchida, N. Yoshinaga, K. Yanagihara, E. Yuba, K. Kataoka, K. Itaka, Designing
immunostimulatory double stranded messenger RNA with maintained translational
activity through hybridization with poly A sequences for effective vaccination.
Biomaterials 150 162-170 (2018)

NanoSky VOL.06 DECEMBER 2018

| 11

Listen to

COINS'
Members

Miki MASAI
Works on research every day to provide
drug delivery system (DDS) for nucleic acidmedicine for the world.

S vation Center of NanoMedicine, theince 2016, I have worked for the Inno-

core organization of COINS. At first, it was
surprising for me that a leading-edge institute exists in an industrial region. Although I
have lived in Kawasaki since early childhood, I did not know about the Innovation
Center of NanoMedicine or even the construction of a new research town called KingSkyFront either. The former factory sites
have been converted into a new town completely different from the previous one.
I currently engage in research of nucleic
acid medicine and study every day for thegoal of treating cancers, such as brain tumors, rare diseases, as well as various dis-Researcher, Research and Development
Division, AccuRna Inc.

Nucleic acid medicine leads to global
KAWASAKI
eases in the future. Nucleic acid medicine is
the next-generation medicine using nucleic
acid, such as DNA and RNA. This field has
markedly progressed in recent years, suchas a short-chain nucleic acid called siRNAthat was approved as a pharmaceuticalproduct in the US in 2018. However, nucleic acid is very unstable and is still difficult todeliver to the disease target securely, posing
a lot of problems. Thus, our company fuses
the excellent technology of Dr. Kazunori
Kataoka, the research supervisor of COINS,
with nucleic acid technologies from pharmaceutical companies and universities aroundthe world, seeking to create a new nucleic
acid medicine and launch it to the world.

Daniel Gonzalez Carter

My secret goal in the future is to launchin-body hospital and nucleic acid medicine
that COINS isseeking to theworld, making
Kawasaki famous as global Kawasaki.

With colleagues

Research Scientist

Challenge big health problems with a small
solution
L to join the Kataoka lab in the Innovaast year I had the great opportunity

tion Center of NanoMedicine. I was reallyexcited to take up this opportunity to workin Japan not only because of the great
work and scientific innovation being doneat the Kataoka lab, but also to be able toexperience the culture of Japan. I have always enjoyed travelling and experiencing
new places. After leaving my home country of Mexico at the age of 15, I lived invarious countries around the world, including the United States, France and England. I’ve also had the opportunity to explore some very amazing places, like thesouthern wetlands of Brazil, the rainforests

12 | NanoSky VOL.06 DECEMBER 2018

What wof Costa Rica, and cycling across theShetland Islands. Therefore, coming to theland of the rising sun was a really excitingprospect.
Having now lived almost two years inJapan, I find that the experience itself has
aided my scientific research. In order toovercome the problems facing our research, scientists have to be creative andable to think outside the box. This is best
achieved if the mind is properly stimulated.
The culture clash I have experienced living
in Japan has definitely kept my mind stimulated, whether it is simply trying to decipher kanji characters in the bus or navigating the complex etiquette of this culture. I

Treatment of a brain disorder such as Alzheimer's
disease has been found impossible because it
is not possible for drugs to enter the brain. I am
using nanocarriers for actively invade the brain
and protecting neurons for treatment that could
stop the progression of Alzheimer's disease.

will definitely remember my stay here withgreat fondness for the rest of my life and I
believe will greatly aid me in my scientificadvancement.

e treasure
Takuya ISHIIManager of Kawasaki Research Insititute, Div. of
Pharmaceutical Research, SBI Pharmaceuticals, Co., Ltd.

Beyond the imagination
I while I was observing an operation in thethought“I wish the cancer emitted light!”

Hospital Training Program in my school days,
where I wanted to be a clinical engineer in the future. At that time, I did not imagine that this would
be put into practical use in years, or even that I
would work on the research of this subject as a researcher of a pharmaceutical company engaging
in the research. Visualization of cancer is one of
the great issues of the diagnosis and treatment ofcancer.
5-aminolevulinic acid (ALA) is a natural occurring amino acid and a precursor of biosynthesis ofporphyrin that is important in the biological activityof animals and plants. Porphyrin is the source ofchlorophyll in plants and heme in animals.

On the other hand, administration of ALA tocancer cell causes the accumulation of porphyrins
that are metabolite of ALA and can emit red fluorescence when irradiated with blue light. This
property has already been put into practical use asa cancer imaging technology with ALA, which iscalled photodynamic diagnosis (PDD) in neurosurgery and urology. Furthermore, cancer can betreated with photodynamic therapy (PDT) that irradiates cancer cells with red light after administration of ALA. Linking these technologies finally enables minimally invasive diagnostic and therapeutic
systems that integrate diagnosis and treatment
with the combination of ALA and light.
We moved from Kobe to Kawasaki (iCONM) in2018 and have participated in COINS since then.

Samuel Crowley
I develop mRNA as regenerative medicine totreat problems like spinal cord injury.

I Savannah, Missouri in the middle
was raised in a small town calledof the United States of America. The
city had a population of less than 5000
people. My family has owned a farmnear the town since the 1830s, where
we raise cattle. I hope to eventually return to the farm and help my family withthe work.
I received my bachelor’s degree in
Chemistry from Missouri Western State
University in St. Joseph, Missouri in2009. I received my Ph.D. in Medicinal
Chemistry from the University of Iowa
College of Pharmacy in 2015. It was in
Iowa where I first began working with

Studies minimally invasive diagnosis/treatment ofcancer with a combination of ALA and light

As the environment for experiments was eventually
established, we will accelerate the research, and I
will contribute using ALA to achievement of smart
life care society proposed by COINS.

The landscape of Kobe from Rokko Mountain. It was abeautiful seaport town.

Visiting Scientist (Tokyo Medical and Dental
University)

Family History and New Technology
nanomedicine and mR NA delivery. I
came to Japan in 2015 to join Keiji Itaka’s group and continue to use mRNA
as a therapeutic. Specifically, I havebeen using mRNA to treat
Spinal Cord Injury inmice. I have also been
exploring alternative types
of mRNA that will hopefully extend the time thatthe mRNA can produce
protein after delivery.
While in Japan I hope
to visit Hokkaido. While
Tokyo is a nice city, it is
far more crowded than I My family's farmam used to, and seeing Hokkaido will remind me of home.

NanoSky VOL.06 DECEMBER 2018

| 13

ACTIVITY REPORT
10th General Meeting～ Bring unity toward the final phase III ～10th General Meeting was held at the Kawasaki Life
Science and Environment Research Center (LiSE) on
Tuesday, June 19, 2018.
Since this fiscal year is the final year of Phase II (Heisei 28-30), with the realization of“in-body hospitals”in mind, we
confirmed the progress of research, social implementation andplans for phase III (Heisei 31–33) with awareness of thedifferentiation / advantage from the existing technology. In thepanel discussion, we shared the determination to the phase III
and also discussed on the tasks for promoting the project. In
addition, COINS research promotion office introduced thechallenge of COINS members to“research group cloudfunding”which is a new effort at iCONM. Moreover, Mr.
Yasuhiro Otomo, Deputy Director, Medical New Technology
Strategy Office, Nitto Boseki Co., Ltd. that newly participatedin COINS after moved in iCONM introduced the company. In
poster session, there were 31 presentations and very active

discussions were carried out among the researchers. Finally,
Mr. Toshio Asano, Asahi Kasei Corporation, Mr. Hiroshi
Misawa, Medical Technology Association of Japan and Mr.
Masafumi Nogimori, Mr. Haruhiko Manabe, JST gave us
feedback that we should always aware of step-up to social
implementation, hoping to work with speed while catching up
market and other people’s trends. The meeting was very
productive to further strengthen the tie of the researchers.
This time, in cooperation with the National Institute of Health
Sciences, we were invited to visit a facility just opened in
March this year at King SkyFront as iCONM. Also because it
was still charged up after the visit to NIHS, it became very
fruitful opportunity that we could feel the breakthrough of
COINS in phase III as there were active comments on regional
collaboration and industry-university cooperation as future
development.

Mr. Masafumi Nogimori ,JSTdelivers feedback.

Poster session scene

TopicsJanuary – June 2018

◦1.7.2018【News】Dr. Kazunori Kataoka, COINS Research Leader, appeared on TBS TV“Saturday Morning”. In-body hospitals and Nanomachines were introduced.
◦1.11.2018【News】The article about the research of Dr. Yasutaka
Anraku, Project Professor, Department of Bioengineering, Graduate School of Engineering, The University of Tokyo was posted on page5, Nikkei Sangyo Shimbun. The title was“Nanoparticles give light formental illness medicine, BBB-crossing nanomachines enter the brain via
a systemic route - lead by leaders of next generation”.
◦1.17.2018【News】This is summary of COINS research team was posted on website of Nature Communications. The title was “Developmentof "BBB-crossing nanomachines which enter the brain via a systemicroute by efficiently reach neurons for glycemic control”.
◦1.24.2018【News】Dr. Kazunori Kataoka, COINS Research Leader’s seminar scene was introduced on Okayama University’s website. The
title was“President’s Top Seminar was held by our invited speaker, Dr.
Kazunori Kataoka, Vice-Director of Kawasaki Institute of Industrial Promotion”.
◦1.25.2018【Activity】9th COINS General Meeting was held.
◦1.28.2018【Appoint】 Dr. Kazunori Kataoka, COINS Research

14 | NanoSky VOL.06 DECEMBER 2018

Leader was appointed to Associate Editor of ACS Nano published byAmerican Chemical Society.
◦2.5.2018【Activity】 COINS Seminar #29 was held at iCONM.
Lecturer: Prof. Tatsuya Shimizu, Director, Institute of Advanced BioMedical engineering and Science Tokyo Women’s Medical University /Title: Current status and outlook of regenerative medicine research using cell sheets◦2.16.2018 【Activity】 COINS Seminar #30 was held. (Article→p.16) Lecturer: Prof. Sei Kwang Hahn, Department of Materials Science and Engineering at POSTECH, KOREA / Title: Smart Photomedicines Using Multi-Functional Nanomaterials◦3.2.2018【Activity】 COINS Seminar #31 was held. 1) Lecturer: Koji Suzuki, Director JSR Corporation, Research & Development
Division, JKiC / Title: overview of JSR-Keio University Medical andChemical Innovation Center (JKiC) 2) Lecturer: Hideyuki Saya, Professor, School of Medicine, Keio University / Title: Development of therapeutic strategies targeting cancer heterogeneity and microenvironment◦3 .10 . 2 0 1 8 【N e w s】 D r. K a z u n o r i K a t a o k a , C O I N S R e s e a r c h
Leader’s lecture at Yomiuri Techno Forum was introduced on YOMIURIONLINE. Title was“Micro capsule, Target cancer cell ….Research treatment”.

Activity Report◦3. 21. 2018 【News】Dr. Kazunori Kataoka, COINS Research Leader
appeared on TV Tokyo“ Yugata satellite”.
◦3.27.2018【News】 iCONM & COINS, our main project was i n troduced on Kanagawa Shimbun on P.14. Title was“Kawasaki Mirai
Shimbun vol.4 Creation of new town for the future / Power to create afuture / Future Keihin Coastal area aims for”.
◦4.1.2018【News】 Interview of visiting scientist, Dr. Shigehito
Osawa (Assistant professor, Tokyo University of Science) was posted
on Kawasaki city Shiseiyouran2018. Title was“People of Kawasaki
Passion x Unity”/No.3 Technology Hope to create medicine from KingSkyFront◦4. 24 . 2018【Activity】COINS Seminar #32 was held. (Article →p.16)
Lecturer: Dr. Takao Inoue, Chief of laboratory, National Institute of
Health Sciences Title:“Trend of development and regulation of oligonucleotide therapeutics”◦ 4. 27.2018【News】The interview of Visiting Scientist, Dr. Yasutaka
Anraku (Assistant professor, The University of Tokyo) was introducedon Kawasaki Shisei Dayori. Title: The future starting from the coastal
area Under the research on nanomachines that deliver the drug to brain
is on the way◦5.14.2018【News】 The interview of Director General, Dr. Kazunori Kataoka (Professor, The University of Tokyo) was introduced on
Shuukangendai. Title was“Photo reportage: Mankind overcomes『cancer』by Nanomedicine”◦5.14 .2018【Activity】COINS Seminar #33 was held. Lecturer : Dr.
Mariko Shiba, Director, National Cerebral and Cardiovascular Center
Title: "Development of antisense drug targeting refractory dyslipidemia”◦5 . 21. 2 018 【N e w s】 R e s e a r c h L e a d e r, D r. K a z u n o r i K a t a o k a(Director General of iCONM, Professor, The University of Tokyo)’s interview was posted in academist Journal. Title was“Make Kawasaki City
the hub of Health kombinat! – Aim to realize a“In-body hospitals”where
nanomachines go around the body –Challenge cloud funding◦5.25.2018【Activity】iCONM opened Twitter and Facebook.

Twitter →Facebook→◦5.28.2018【Activity】 COINS researcher Mr.Takuya Miyazaki ischallenging crowd-funding as part of research towards the realizationof “In-body hospitals”. Title was“Treat pancreatic cancer at pinpoint”.
◦6.10.2018【Activity】 COINS Seminar #34 was held. Lecturer:
Mr.Toshio Nagae, Pharma Business Consultant, PeptiDream, HMT /Representative, Audit & Supervisory Board Member Title:“Value Optimization of JP-origin Drugs/DDS, Issues and Alternative Solutions”◦6.12 . 2 018【News】COINS Research Leader, Dr. Kazunori Kataoka (Director General of iCONM, Professor, The University of Tokyo)’s interview was posted on Nikkan Gendai. Title was“Featured healthcare that supports 100 years of life - Realization in as early as 3 years.
Virus-sized medical robot treats cancer and dementia = Eventually“Inbody hospitals”.
◦6.19.2018 【Activity】10th COINS General Meeting was held.
(Article →p.14)◦6.24.2018【News】Research Leader, Dr. Kazunori Kataoka (Director General of iCONM, Professor, The University of Tokyo) appearedon TV program BS Fuji“Galileo X”. He talked about the potential of Inbody hospitals for Alzheimer's disease. Title was“Prevention of dementia”.
◦6. 25. 2018【Activity】 Sabina Quader, iCONM scientist (COINS
theme 1 & 2) challenged crowd-funding Theme was“Glioblastoma
Multiforme treatment”.(Article →p.15)◦6.26.2018 【Award】 Mr. Naoto Yoshinaga (Trainee of iCONM,
The University of Tokyo) received The Best Oral Presentation Award
from the 34th Annual Meeting of the Japan Society of Drug Delivery
System.

～ Part of activities to realize“in-body hospitals”
such as human resource development and outreach ～For further accelerating research to realize“in-bodyhospitals”, It is important that researchers take initiative to work
even more active.Especially for young researchers who will be
responsible for the future, they need the ability to think about
the next research theme by themselves, communicate theirsignificance in an easy-to-understand manner, receive various
support and opinions, and advance research alongside them.
As an implementation of human resource development, westarted cloud funding. This time, Dr. Sabina Quader, SeniorResearch Scientist and Mr. Takuya Miyazaki, D3, Departmentof Engineering, Graduate School of Engineering, The Universityof Tokyo launched a site at academic cloud funding site
“Academist (Academist)”with the aim of developing
nanomachines for cancer that is difficult to treat such as
pancreatic cancer and brain tumor. Although they were both
puzzled by the fact that this was the first time, they had many
meetings with the person in charge of the Academist andseriously thought about how to disseminate information to tell
the people of the world what they wanted to do. As a result, thesite received many comments of approval and expectation. The
two challengers got more learning than the success or failureof acquisition of research funds, and it was a good opportunity
for let more people know about“in-body hospitals”as well.

Dr. Sabina Quader’s siteDr. Miyazaki’s siteNanoSky VOL.06 DECEMBER 2018

| 15

Activity Report
COINS Seminar Report～ From King SkyFront (Region)
towards Construction of Global collaboration ～〈COINS Seminar #30〉
On Monday, February 16, Professor Sei Kwang Hahn (Department ofMaterials Science and Engineering) of Pohang University of Technology( P OST EC H ) in Korea gave a lecture. U nd er the theme of S mar t
Photomedicines using Multi-Functional Nanomaterials, he introduced
development status of the latest Smart Photo Medicine for further biologicaland medical application. Many researchers from various universities andresearch institutes joined on the day, and discussions after the lecture andbusiness card exchange were actively performed. The seminar was very
successful.
POSTECH is a high-level research institute where pioneering research inth e field of scie n ce a n d te ch n olog y a reconducted , and at the same time it is aremarkably growing university as it became the
top ranking in world university rankings
Professor Hahn’s technology is also importantin the realization of“in-body hospitals”and thediscussion among the researchers which washeld before the seminar was also heated up. We
anticipate that further collaboration between
POSTECH and iCONM will progress with thisassociation.
Prof. Sei Kwang Hahn

Anticipate collaboration with Prof. Hahn

〈COINS Seminar #32〉
On Tuesday, April 24, Mr. Takao Inoue, Director, Division of Molecular
Target and Gene Therapy Products, National Institute of Health Sciences(Nucleic Acid Pharmaceutical Affairs Division) gave lecture at the Kawasaki
Life Science and Environment Research Center (LiSE). (Reference: NL p.2―
5 talks). There were many participants from companies, universities, research
institutes, etc., and we could see that it was on going high-profile.
In the lecture on“Development Trend of Nucleic Acid Pharmaceuticals
a n d Current Status of R egulator y I m provement ”, outline of basic
characteristics, classification, action mechanisms, development trends, etc.
of nucleic acid drugs and concept of quality / safety evaluation peculiar to
nucleic acid drugs were introduced. Active discussion continued until at thereception party.
Currently, the National Institute of Health Sciences and iCONM are locatedin the same Kawasaki City King SkyFront area. We hope that this seminar isalso a starting point that collaboration will progress with respect to the
medicine of nucleic acid medicine and mRNA.

Prof. Takao Inoue

Editor’s NoteThose who read the past issue of "NanoSky" (vol. 2 ― 5) may have felt a little odd in the contents of this vol.6.
The themes of COINS that we have covered so far have the strong image of using the DDS function of nanomachines to deliverdrugs to the target pinpoints and attack the cells / tissues and treat. However, the theme 3 of this journal is completely opposite.
DDS is essential, but rather than pursuing its emphasis on medicating the mRNA of its contents, it is oriented toward treatment
based on normalization and activation of existing cells, not attacking on cells.
Theme 3 has been working on mRNA drugs ahead of the rest of the world and not only promoting research, but also establishingoutreach and venture in cooperation with other organizations, social implementation is progressing in parallel at the same time.
It may be because of that reason, the tone at the talks (p. 2 ― 5) was modest or realistic at the place, but we could feel their
enthusiasm for sending out to the world to contribute for society. It seems that there are still few people with the same intention in the
country yet, but we hope“NanoSky”will be able to contribute that it will grow into a big business which will save people in need andeven the Japanese economy.
（Editor-in-chief Takashi Sugimoto）

6

Edited by NanoSky Editorial Board (Keiji Itaka, Takashi Sugimoto,
Miyako Yokoyama)
Writer： Ayumi KOJIMA
Camera : Kazuyuki OTSUBO
Design : Studio L Co., Ltd. Studio R Co., Ltd.
Copyright : KAWASAKI INSTITUTE OF INDUSTRIAL PROMOTION

Vol.

Published by Center of Open Innovation Network for Smart Health (COINS),
Innovation Center of NanoMedicine (iCONM),
KAWASAKI INSTITUTE OF INDUSTRIAL PROMOTION,
3-25-14, Tonomachi, Kawasaki-ku, Kawasaki City, Kanagawa Pref. JAPANTEL: +81 44 589 5785 / FAX: +81 44 589 5789
http://coins.kawasaki-net.ne.jp/