Researchers develop a mRNA-based gene therapy for osteoarthritis

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Researchers affiliated with the Kawasaki INnovation Gateway at SKYFRONT, Kawasaki City, Japan have developed a new mRNA-based gene therapy that could become the first disease-modifying osteoarthritic drug system for use in clinical practice. The findings were published in Nature Scientific Reports, January 2016.

Researchers have established a new therapy for the treatment of osteoarthritis, in which messenger RNA was directly introduced into the joint to trigger new cartilage formation.

The researchers hope this study will lead to a new osteoarthritis therapy.

mRNA-based gene therapy for osteoarthritis
Osteoarthritis (OA) is a chronic, painful and debilitating condition affecting elderly people across the globe. It is an age-related change but often accelerated by joint instability, inducing cartilage degradation. However, current therapies are limited to symptomatic medications to reduce inflammation and pain, and there are no disease-modifying therapy of OA.

Now, Keiji Itaka (Principal Research Scientist of Innovation Center of NanoMedicine, Kawasaki City) and co-workers at the University of Tokyo’s Graduate School of Medicine and the Graduate School of Engineering have developed a new gene therapy that could become the first disease-modifying osteoarthritic drug system for use in clinical practice.

The team wanted to deliver a cartilage-anabolic factor called RUNX1 directly into joints. RUNX1 is a transcriptional factor known to stimulate chondrogenesis – the formation and maintenance of cartilage by cells called chondrocytes. The use of messenger RNA (mRNA) is a new technology to deliver the transcription factor. Besides the high capacity of mRNA to introduce the factor into chondrocytes, mRNA has an important aspect of safety – the mRNA would not be integrated into the genome (DNA) or cell nucleus, avoiding unwanted mutations and oncogenesis.

To deliver the mRNA to the target joint, the researchers created a carrier polyplex nanomicelles – possessing the mRNA in the nanomicelles and releasing it in the joint. They tested the mRNA-loaded nanomicelle system on the mouse model of knee OA. The RUNX1 mRNA was injected every three days for a month into the knee joint.

Itaka’ team found that, compared with control mice that were not treated, the progression of OA was significantly suppressed in the mRNA treatment group. The articular chondrocytes in the treated knees exhibited high activity of cartilage synthesis than those in the control group.
The researchers hope this study will lead to a new OA therapy.

Reference and affiliations
H. Aini1, K. Itaka1, A. Fujisawa2, H. Uchida1, S. Uchida1, S. Fukushima4, K. Kataoka1,4, T. Saito3, U. Chung1,2& S. Ohba2.Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment. Nature Scientific Reports 6 (18743) (2016)
1.    Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
2.    Department of Bioengineering, The University of Tokyo Graduate School of Engineering, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
3.    Department of Bone and Cartilage Regenerative Medicine and Department of Sensory and Motor System Medicine, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
4.    Department of Materials Engineering, The University of Tokyo Graduate School of Engineering, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

About KING SKYFRONT

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 launched in 2013 to focus on open innovation in the life sciences and environment.

July 2016 issue of Kawasaki SkyFront iNewsletter

http://inewsletter-king-skyfront.jp/en/

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=24Y2VFBOD8c&list=PL70Lb7fKyWsjegtd4tBfXQqbRZbeNjqwt&index=2
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: 59jigyo(at)city.kawasaki(dot)jp

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Naoko Sato
Kawasaki City
+81 9065213797
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