Bacteriophage (hereinafter abbreviated as "phage") is a type of virus that infects and proliferates a specific bacterium, lyses (kills) the bacterium with a lytic enzyme, releases daughter phage, and its existence has been known since the early 20th century.

Phage T4 in the figure is one of the seven most studied (T1-T7) E. coli phage.

Before the phage was officially discovered, bacteriologists in the 1890s had already observed unidentified substances that might have limited bacterial activity. In 1915, British bacteriologist F. Twort (1877-1950) discovered phage from staphylococci, and in 1917 Canadian microbiologist F. d'Herelle (1873-1949) discovered phage from Shigella.

Since that time, phage research has begun to kill causative organisms for the treatment of infectious diseases.

It is said that more than 1031 phages exist on the earth, and phages exist anywhere on the earth where bacteria exist, for example, they also inhabit the human intestine and epidermis.

Although phages come in a variety of sizes and shapes, most have the same basic characteristics.

Although it is described as looking like an Apollo spacecraft that landed on the moon, it has a strange appearance that gives a very artificial atmosphere, a simple consisting of a `` head '' storing genes and `` legs '' capturing bacteria, and each has a specific structure, each of which attacks specific bacteria.

Since it infects only the host bacteria, the host range (spectrum) is relatively narrow and does not affect the non-target bacteria.

That is, E. coli phage does not infect staphylococci or Bacillus and vice versa.

Bacteria can acquire resistance to certain phages.

However, a new phage that the bacteria do not have resistance can be further isolated, and the phage can also evolve.

In addition, multiple phages can be used as a cocktail to suppress phage resistance.

Phage has been studied extensively mainly in the former Soviet Union and Eastern Europe, but since it is effective only for specific bacteria, research on phage has decreased due to the emergence of antibiotics that can respond to many infectious diseases, especially in the West.

The emergence of this antibiotic has overcome the terrible infectious diseases that have killed many humans, such as sepsis and tetanus, and have dramatically advanced modern medicine. Antibiotics, called "miracle drugs," were effective against a variety of infectious diseases, but were eventually used in large quantities, resulting in resistant bacteria that could not be killed with antibiotics, and now, how to deal with drug-resistant bacteria is becoming a big problem.

Phage therapy using phage has been practiced in eastern countries such as Russia, Georgia (now Georgia), and Poland for a long time, and is currently being pharmaceuticalized in those countries.

Phage R & D has been activated in the United States and Europe in the latter half of the 2010s, following a case in the United States where phage treatment showed dramatic therapeutic effects.

A phage and antibiotics were simultaneously injected into a man infected with a Pseudomonas aeruginosa bacterium that is highly resistant to antibiotics from an artificial blood vessel used in heart surgery.

As a result, a few weeks later the infection was cured.

However, the number of clinical studies is limited, and phage therapy is in the research stage and has not yet reached practical use.

In addition to medical use, practical use has begun in fields such as food safety.

Application to Listeria monocytogenes.

When a person becomes infected with Listeria monocytogenes, healthy adults often end up with mild gastrointestinal symptoms or asymptomatic. However, the elderly, immunocompromised, infants, etc. may suffer from severe symptoms such as meningitis and sepsis, and the fatality rate is said to be 20-30%.This phage preparation against Listeria monocytogenes has already been formulated in the United States as a safe product approved by the US Food and Drug Administration (FDA).

This phage product has emerged because it is easier to be approved as a food ingredient or additive than it is to be a pharmaceutical, and the need for new innovations that reduce the risk of food contamination.

However, phage products have only recently appeared on the market.

Thus, in the latest global trend, phage preparations will be used not only as human medicines but also as quasi-drug disinfectants and veterinary medicines. If progress is made, it will play a part in the antibacterial agent market, and development competition has begun in each country.

Murakami, the representative of our company, constructed a high-performance phage display library in a study on a rapid development method for high-stable VHH antibodies which is one of the base technologies in our company.

In this study, he examined the application of natural phage, and discovered the potential of phage therapy using phage characteristics as an antibacterial agent replacing antibiotics.

Therefore, we have started the phage business with one of the objectives of providing the knowledge that will not be used effectively as it is and will be stored inside the university widely to society in the form of new goods and services and increasing the public interest.

Okinawa Prefecture, where our company is located, is dotted with large and small islands in the sea area spanning about 1,200 km, and it is thought that a variety of phages are latent due to the subtropical climate and humid environment, so that we thing Okinawa is the best place to search for natural phage.

Now, we are promoting the banking of phages latent in the islands of Okinawa using our unique know-how of phage collection, and we are conducting research and development to isolate a total of more than 1,000 natural phage that are effective against clinical strains and ATCC strains of Pseudomonas aeruginosa, Staphylococcus aureus and enterohemorrhagic Escherichia coli by the spring of 2020.

(600 phages have been banked: 2019/9).

Furthermore, in order to verify the usefulness of the isolated phage, long-term storage stability tests and verification of the bactericidal effect by animal experiments are underway. We have also begun developing more efficient multi-species co-culture systems and preparing for clinical trials in collaboration with clinicians.

The goal of this business is to develop antibacterial drugs using phage, vaccine materials, reagents for detecting bacteria, quasi-drugs and supplements, and apply them to livestock and aquaculture.

In pursuing this business, we are looking for joint research with companies that will become alliance partners and universities and research institutes for development.