Interview with Yoshinari Yamamoto, Assistant Professor
In the world today, there is increasing interest in health. Nanoencapsulation of oligodeoxynucleotides, one of the useful functional materials, helps the material to be used more easily, leading to prevention and alleviation of diseases through oral administration. The exploration of unknown functions will continue.
Making Full Use of Immunostimulatory Components of Microorganisms for Promoting Health
  These days, “functional material” is a subject often featured in the media. Materials with properties that have favorable influence on the human body are called functional materials.

Dr. Yamamoto researches the feasibility of using components of microorganisms as functional materials. The subjects of his research include cell wall components, flagella ingredients, and nucleic acid components like deoxyribonucleic acid (DNA).

“When you hear the term ‘microorganism’, what comes to mind may vary, ranging from coliform bacteria and other malicious microorganisms that cause diseases, to lactic acid bacteria and other microorganisms conveying a good impression. It is known that every component obtained by decomposing these microorganisms has a different mechanism of stimulating immune functions,” explains Dr. Yamamoto.
The bodies of mammals and fish are naturally equipped with a biological defense mechanism, namely, the immune system, that helps maintain their well-being. Therefore, it is said that an imbalance in the immune system causes a cold, a tumor in the body, an allergy, or an inflammatory disease.

“In other words,” continues Dr. Yamamoto, “the effective use of microorganism components with immunostimulatory properties can help improve our health.”

What Dr. Yamamoto specifically selects as a sample for his research is oligodeoxynucleotides. According to Dr. Yamamoto, oligodeoxynucleotides are functional molecules derived from bacterial DNA sequences, attracting attention as a next-generation nucleic acid-based drug.

“It is a known fact that DNA contains genetic information. In addition, it has been found that, when cells are exposed to or animals are injected with microorganism-derived DNA, immune functions can be controlled, resulting in the prevention and alleviation of various diseases.”

Since the discovery of oligodeoxynucleotides about 20 years ago, it has been reported that they can help prevent or alleviate a wide range of disorders. Dr. Yamamoto’s research has also proved that injections of a type of oligodeoxynucleotides can alleviate the aggravation of sepsis due to bacterial infection.
Oral Administration of Nanoencapsulated Oligodeoxynucleotides Produces the World's First Achievement
  Although it has been reported that oligodeoxynucleotides are useful in various cases, major methods of administration to a living body used to be limited to injections and nose drops. Given these circumstances, Dr. Yamamoto became interested in oral administration that may reproduce the same effects.

“I started this research when I was studying for a master’s degree. When I first encountered oligodeoxynucleotides, the fact that DNA itself controls immune functions was a novelty for me. Since then, I have become more and more absorbed in oligodeoxynucleotides.”

Oral administration causes no stress on a living body. Unfortunately, however, oligodeoxynucleotides are considerably sensitive to acids and alkali. This vulnerability causes oligodeoxynucleotides to be broken down by stomach acid before they reach the intestines.
“To address this issue, I hit upon the idea of encapsulating oligodeoxynucleotides by using calcium harmless to a living body.”

In subsequent experiments, Dr. Yamamoto succeeded in delivering oligodeoxynucleotides, which escaped being broken down by stomach acid, to the intestinal immune system by orally administering freeze-dried encapsulated oligodeoxynucleotides. Their activity was also observed. Furthermore, it has been confirmed that oral administration of oligodeoxynucleotide capsules to mouse models of atopic dermatitis alleviates the symptoms.

The invention of wrapping oligodeoxynucleotides in calcium nanoparticles has enabled the largest weakness of oligodeoxynucleotides, decomposition in stomach acid, to be overcome. Moreover, Dr. Yamamoto’s research has proved that, instead of an unprofitably large amount of oligodeoxynucleotides, which was orally administered in previous research, the long-term administration of a small amount of encapsulated oligodeoxynucleotides can control immune functions. This is highly regarded as the world’s first research report of this kind.
 Development of DNA nanocapsule (DNanocap)
Seeking the Moment of Discovering the Unknown – Never Stop Challenging

  “The oligodeoxynucleotide that was effective against sepsis in my research was discovered by coincidence from among many sequences of oligodeoxynucleotides. It was a product of chance. Therefore, I believe that oligodeoxynucleotides still have plenty of attractive functions and possibilities for application for us to explore,” said Dr. Yamamoto.

He tells with a smile that the real excitement of research is to enjoy the moment of discovering a totally unknown phenomenon.

At present, Dr. Yamamoto continues his research with an eye toward using oligodeoxynucleotides as livestock feed. Under circumstances where concerns are rising over livestock infectious diseases, including avian influenza and swine fever, it can be expected that livestock feed containing encapsulated oligodeoxynucleotides will keep increasing immune strength all the time, enhancing resistance to infectious diseases.

Another focus of his study is the influence of oligodeoxynucleotides on intestinal bacteria whose relationship with many lifestyle-related diseases has been reported. Dr. Yamamoto is enthusiastic about demonstrating and elucidating the influence.

“I am eager to continue my research with the objective of utilizing oligodeoxynucleotides to promote human and livestock health,” Dr. Yamamoto said, expressing his aspiration. Besides his research, he considers it another important mission to produce next-generation experts who will play a leading role. Dr. Yamamoto calls out to young people to participate by saying as follows:

“It is true that recent few years have seen dramatic advances in environments for our health and well-being. With the establishment of prevention and treatment methods for various diseases, a 100-year-long life is often on our lips. However, there still are numerous diseases without cures around the world and details of disease mechanisms are yet to be elucidated.
Research has a very monomaniacal aspect, sometimes requiring patience. What is indispensable for the development of science is your exuberant energy, namely, the power of bearers of the next generation. Why not achieve what no one else has with us by employing your untiring energies in research?”
Yoshinari Yamamoto, Assistant Professor
Assistant Professor, Laboratory of Food Chemistry

April 1, 2016 – March 31, 2018:Research Fellow of the Japan Society for the Promotion of Science for Young Scientists (DC2)
April 1, 2018 – :Assistant Professor, Graduate School of Integrated Sciences for Life, Hiroshima University

Published on April 10, 2020