It is becoming increasingly difficult to explore novel small-molecule compounds or antibody drug candidates. Therefore, it is essential to develop new technologies different from conventional methods to acquire lead compounds or lead antibodies.
We are engaged in research aimed at producing new natural products from fungi and creating candidate monoclonal antibodies for antibody drugs using synthetic genome technology. The first involves a technique called the TAQing system, which utilizes conditionally-activated restriction enzymes within living cells, cutting the genomic DNA at multiple sites, promoting large-scale genome rearrangements, and inducing phenotypic changes. We have used this technology to alter the traits of yeast, plants, and filamentous fungi. Applying this system to filamentous fungi enabled induced expression of dormant biosynthesis gene clusters for natural products.
The second approach involves the Human ADLib system using a chicken B-cell line with human antibody genes introduced into the chromosomes. This system enabled production of human monoclonal antibodies against the target antigen rapidly, followed by seamless affinity maturation to levels close to the antibody medicines. Through these two examples, we also want to consider the possibilities of synthetic genome technologies in recent drug discovery.