Creation of Agrofactory - Production of Biomedicine from Animals and Plants -/CRDS-FY2006-SP-16
Executive Summary

This strategic program “Creation of Agrofactory” aims to establish a system that can produce useful proteins for humans efficiently and at low cost in an easy-to-use form by transferring foreign genes regiospecifically into the animal and plant genomes.

Currently, biotechnology-based drugs are manufactured by tank fermentation of animal cells that can cause sugar chain modification close to humans. However, because there are big issues with this method such as limited productivity of cultured cells and expensive facilities such as a culture tank, building of a next-generation production system that can exceed the animal cell culture is expected. Therefore, we propose R&D to create animal and plant individuals transferred with human genes that can efficiently produce biotechnology-based drugs and present specific issues below:

1. Technology to transfer foreign genes into animal and plant genomes
When a molecular weight is a huge protein, the development of a technology to stably transfer the relevant gene to a genome and a technology to transfer it into a specific region of animal and plant genomes is necessary. Therefore, we need to promote the development of a method to transfer a vector inserted with the foreign gene along with the gene transfer vector into the cell without causing any damage.
2. Modification technology of foreign proteins in plant
Even if we can produce the intended protein in a plant body, if the protein does not function as an activated form that has an effect on humans, there will be no value as a drug. A key to this activated form is post-translational modification in the cell. In order to produce a protein close to a human type in the plant, we aim to establish a regulation technology of this sugar chain modification.
3. Regulation technology of protein transportation toward target tissue (organ) in plant
In order to increase yield of transferred proteins, a lot of protein transportation technologies are necessity. In this proposal, we establish a technology to regulate functional differentiation of vacuole and related single membrane organelles, a technology to control transportation of proteins in and out of the cells and a technology to delete deposit proteins.
4. Creation of genetically-modified individual by genesis and regeneration technologies
When enucleated eggs are injected into the cells to which foreign genes are stably inserted, initialization of a somatic nucleus (re-programming) occurs. We aim to develop a technology that improves the efficiency of re-programming that uses a feature in which a small percentage of the somatic nucleus-transferred eggs are generated as an individual body in the host uterus and also examine to develop an in vitro culture technology of eggs used for research.

The promotion of this program enables to establish a low-cost target protein production system. This promotes not only innovation of a manufacturing process for pharmaceutical companies but also advancement of translational research and high-mix low-volume production of orphan drugs. The advanced gene modification technology also makes it possible to create an experimental animal transferred with a gene cluster such as human immune system and it is expected to create a therapeutic model for diseases that can be replaced by conventional experimental animal