-- From the beginning of May Takara starts selling about 400 DNA fragments for cytokine gene function analysis

Otsu, Japan, May 7, 2002 - (JCN Newswire) - Takara Bio Inc. one of Japan's leading biotechnology companies, is pleased to announce that using its unique ICAN^TM isothermal gene amplification technology, it developed a system capable of industrial production of a wide variety of DNA fragments needed to make DNA microarrays.

As the first step, Takara Bio from May 1 has started sales of about 400 DNA fragments that are useful for the analysis of cytokine gene functions.

ICAN^TM (Isothermal and Chimeric Primer-Initiated Amplification of Nucleic Acids) can produce about 10 times the volume of DNA fragments per unit volume of reagents than using PCR (polymerase chain reaction) technology.

DNA microarrays are able to monitor the presence and relative quantities of the many genes expressed in cells at a time. These microarrays are widely used in a range of fields, including diagnostics and other medical areas, fundamental biological research and applied areas.

To produce DNA microarray, though, it's necessary to produce large quantities of a variety of different probe DNA fragments that are complementary to specific genes to be detected.

One million DNA microarray requires the production of about 0.001 g of the required DNA fragments. Accordingly, spotting 1,000 different types of DNA fragment in this manner would require a total of 1 g of DNA fragments. Production at such a huge scale requires industrial technologies and perspective.

"DNA fragments are to the biotechnology industry what semiconductors are to the electronics industry," said a spokesman from Takara Bio. "Customers will be able to combine Takara Bio fragments in which they are interested to create their own DNA microarrays."

DNA fragments can of course be produced in small quantities in the laboratory using the PCR method. However, this method requires cyclical changes in temperature to amplify the DNA. Increasing the amount of reagent solution increases temperature fluctuations, which create difficulties in terms of DNA amplification. Accordingly, the PCR method is not applicable to industrial-scale production of DNA fragments.

In contrast, the ICAN^TM method uses an isothermal amplification technology, which places no restrictions on the volume of reagent solution that can be used and presents no problems with regards to increasing the scale of the production system.

In addition to these benefits, this reaction structure allows approximately 10 times the volume of DNA fragments to be created per unit volume of reagents than the PCR method.

This remarkable performance makes the new method ideally suited to industrial-scale DNA fragment production. The cost to produce 0.001 g of DNA fragments using the ICAN^TM method is 100,000 yen ($777), whereas producing the same amount of DNA fragments using PCR costs about five times more.

Probe DNA fragments on Takara Bio's DNA microarray series, IntelliGene^TM, are produced using ICAN^TM, showing just how well-suited ICAN^TM-produced DNA fragments are to DNA microarray applications.

In the future, Takara Bio intends to use the ICAN^TM method to produce all the probe DNA fragments it needs to deliver DNA microarray products. At the same time, by selling these fragments at a reasonable price, the company aims to accelerate the spread of DNA microarray technology.

A total of 10,000 different types of DNA fragment are to go on sale during the current fiscal year and include DNA fragments already incorporated into IntelliGene^TM from humans, mice, rats, Arabidopsis, Escherichia coli bacteria, and others, as well as others that have not yet been incorporated in this manner.

Takara Bio's DNA production capabilities are second to none, and the company is confident that it can cater to global demand. Sales of 1 billion yen are predicted in three years' time.

Product Overview
Prices
10 mg: 15,000 yen/fragment
100 mg: 50,000 yen/fragment
1 mg: 100,000 yen/fragment

Details
Human cytokine genes and related DNA fragments.
The approximately 400 types of gene fragment contain a region specific to that gene, which have low homologousness and base lengths of approximately 300.
DNA fragments are modified by amination so as to allow solidification to take place through covalent binding towards the solid-phase.

For more information, please contact
Bio-Industry Department
Takara Bio, Inc.
hayashiy@takara-bio.co.jp

About Takara Bio:
Takara Bio is committed to preventing disease and improving the quality of life of people around the world through the use of biotechnology. Takara Bio focuses on three main areas; the development of technology to facilitate biotechnology-related research, biotechnology applications in gene and cell-based therapies, and the development of preventative medicines from plants and traditional foodstuffs. Through strategic alliances with other industry leaders, the Company aims to become a leader in creating innovative technologies and plans to extend its reach around the world.

Glossary
Cytokines:
Cytokines are protein-type chemical compounds that communicate information between cells. Lymphokines such as interleukin, which carry information between lymph cells, and colony-stimulating factors are also included under cytokines. Cytokines are proteins or glycoproteins, and are expressed as distinctive receptors on the surfaces of indicator cells. The physiological activity affected by cytokines, such as cell differentiation and reproduction, are initiated when connections are made between cytokines and cell receptors.

ICAN^TM
The Isothermal and Chimeric Primer-Initiated Amplification of Nucleic Acids method is an isothermal high-efficiency DNA amplification method developed by Takara Bio. Target DNA contained within samples can be detected and amplified isothermally with greater accuracy than existing PCR methods. This functionality allows the diagnosis of infectious and genetic diseases to be conducted much more efficiently and cheaply than they have been to date with PCR methods. Moreover, as temperature changes are not required when reactions are taking place, the reactions in question can be conducted on a much larger scale than with others methods. This allows the technology to be adapted for the industrial production of DNA.

DNA Microarrays
DNA microarray, produced with the spotting method, are composed of a strip of substrate (such as a glass slide), several square centimeters in area, with between several hundred and 10,000 types of DNA fragments attached to them in specific alignments. A truly revolutionary technology, these microarrays allow the analysis of a vast number of genetic expressions with a single operation. Data gained through this single operation is then entered into computers, which allow vast the rate of DNA analysis to be increased massively.

Probe
DNA molecules are composed of double strands of molecules that mutually complement each other. The term probe refers to DNA fragments marked, for example, with fluorescent dyes to be used in hybridization technology, used to search for complementary DNA.

PCR Method (Polymerase Chain Reaction)
The PCR Method uses cyclical heating equipment to multiply the volume of a minute amount of DNA several hundred times over a period of several hours.

These materials were released to the Kyoto Economic Journalists' Club and the Heavy Industry Research Council on April 24.