日本経済新聞　2003/8/4　　　　　　

「RNA干渉」応用競う　遺伝子抑制で難病の治療薬
　　東京医科歯科大　アルツハイマー向け
　　ｉＧＥＮＥ　エイズ薬の開発着手

　アルツハイマー病やエイズ、がんなどの難病を治療する新薬の開発に「ＲＮＡ（リボ核酸）干渉」という新しい還伝子技術を応用する動きが広がってきた。特定の遺伝子を狙い撃ちして病気の原因となるたんぱく質ができるのを妨げる技術で、従来の新薬開発手法よりはるかに効率がよい。実用化に向け国内外の研究機関や企業が激しい先陣争いを繰り広げている。

　ＲＮＡ干渉は、遺伝子がたんぱく質を作る働きを途中で妨害する新技術。病気にかかわるたんぱく質の遺伝子を標的にすれば、どんな難病でも治療できる可能性がある。
　東京医科歯科大学の水沢英洋教授と横田隆徳講師らはＲＮＡ干渉を駆使して、アルツハイマー病治療薬の基礎実験に成功した。
　この病気は神経細胞に老人斑という染みが沈着して発症すると考えられている。研究チームは老人斑を作り出すカギとなるたんぱく質に着目、そのたんばく質のもとになる遺伝子の働きをＲＮＡ干渉で抑え込んだ。細胞実験で効果を確かめ、現在はネズミを使った研究を進めている。
　水沢教授らは全身の筋肉が徐々に衰える難病、筋委縮性側索硬化症（ＡＬＳ）の治療でも成果を上げた。ＡＬＳの患者は、悪玉の活性酸素から神経細胞を守る働きをする遺伝子に変異がある。ＲＮＡ干渉を活用してこの変異遺伝子を抑え、正常な遺伝子だけを働かせるのに細胞実験で成功した。
　アルツハイマー病やＡＬＳは根治の手立てがない難病。「今後、脳など狙った場所でＲＮＡ干渉を起こす薬を開発できれば、画期的な治療法となる可能性もある」（横田講師）という。
　東京大学の多比良和誠教授らが今春設立したベンチャー、ｉＧＥＮＥ（アイジーン、茨城県つくば市）はＲＮＡ干渉を利用してエイズ治療法などの開発に着手する。エイズウイルスが人間の細胞に感染・増殖する際、何らかのたんぱく質がかかわっているとみられており、ＲＮＡ干渉を使ってこのたんぱく質ができないようにする。
　同社はＲＮＡ干渉の効果を高める独自技術を保有。これを武器に月内にも国内の製薬企業と共同研究契約を結ぶ。久光製薬子会社のジェノファンクション（つくば市）もＲＮＡ干渉を使って高血圧や糖尿病などに関係する遺伝子の探索を計画している。

２年で急速に普及　特許囲い込みの動きも
　ＲＮＡ干渉の応用研究が急速に広がるきっかけとなったのが、独マックス・プランク研究所のトーマス・トウシュル博士（Thomas Tuschl 現・米ロックフェラー大学）らが２００１年に報告した研究成果だ。当初、線虫など限られた生物でしか使えないとされていたが、わずかな工夫で人間の細胞でも引き起こせることを発見。病気治療などに活用する道を開いた。
　それからわずか２年でＲＮＡ干渉は遺伝子の機能解析などで不可欠な手段になった。英ネイチャーなど世界の有力科学誌は、ＲＮＡ干渉を使わない論文は査読の段階で再実験を求めているという。遺伝子の機能を抑える実験ではほかに信頼性が高い手法がないからだ。
　臨床応用への課題の一つは「人工のＲＮＡ分子を患部に的確に送り届けて働かせるベクター（運び役）の開発」（多比良教授）で、各国の研究者が激しく競っている。
　歴史の浅い技術なので重要特許をどの研究機関が押さえているのか、はっきり分からない。トウシュル博士らが名を連ねる米アルナイラム製薬Alnylam Pharmaceutical と、この分野で有力な独ベンチャー企業が合併するなど、特許を囲い込む動きも出ている。

2001/4/25　　産業技術総合研究所

■ 産総研の技術シーズを活用したベンチャー設立に向けた支援

１．独立行政法人 産業技術総合研究所【理事長 吉川 弘之】（以下「産総研」という）の開発した遺伝子機能を解析する技術を活用するベンチャー企業　株式会社ジェノファンクション【代表取締役社長 野沢 　巌 TEL:029-837-2461】（以下「ジェノファンクション社」という）を　久光製薬株式会社（以下「久光製薬」という）が設立し、４月２５日、銀行倶楽部（千代田区大手町　銀行協会ビル内）において、会社設立報告会が行われることとなりました。

２．ジェノファンクション社が事業化を目指す技術は、産総研・ジーンディスカバリー研究センター【センター長 倉地 幸徳】の多比良 和誠（たいら かずなり） 副センター長が開発したリボザイムを利用した遺伝子機能解析技術と久光製薬が持つベクター利用技術を応用することにより、未知の遺伝子機能を明らかにするものです。本技術の事業化によって、遺伝子を利用した新たな医薬品開発が飛躍的に加速されることが期待されます。

３．産総研が有する遺伝子機能解析技術に係わる特許の円滑な実施を図るために、ジェノファンクション社と産総研は共同研究を実施し、産総研が持つノウハウの供与、産総研の高度な試験研究施設の提供等のベンチャー創業に向けた支援を行う予定です。

４．なお、この遺伝子関連技術のほか、産総研はナノテク、ＩＴなど広い技術分野にわたる約１万件の特許等の知的財産権の機動的な移転を推進する技術移転機関（認定ＴＬＯ）である「産総研イノベーションズ」の積極的な活用や、産学官連携の場の提供など、ベンチャーの起業と発展を支援して行きます。

Alnylam Pharmaceuticals　　　 http://www.alnylam.com/company.html

Alnylam Pharmaceuticals is an early-stage therapeutics company. The Cambridge, Massachusetts-based company was founded in 2002 by an international group of scientists that helped discover the novel biological phenomenon of RNA interference. Alnylam's therapeutics focus is on a wide array of human diseases that, to date, are poorly treated by the medical sciences.

Founded on the discovery of RNA interference, Alnylam is developing technology that can specifically and potently silence disease-causing genes. RNA interference is a natural cellular process that combats viral infections by degrading the viral genetic message before it can produce a protein. By adapting this process for therapeutic applications, any pathological gene can be "silenced" without interfering with the gene itself. Thus, RNA interference represents a powerful platform of therapeutics that can treat a diverse range of human diseases.

Alnylam Pharmaceuticals has assembled an internationally recognized founding team and scientific advisory board. In addition, the company has unique access to the critical intellectual property in the field of RNA interference therapeutics. The company is expanding its intellectual property portfolio by developing and patenting methods for the delivery of RNA interference-based therapeutics in a wide variety of diseases.

2003/7/7 Alnylam Pharmaceuticals

Alnylam Pharmaceuticals And Ribopharma Merge To Create Biotechnology Leader In RNA Interference
- Company secures $24.6 million (EUR 21.5 million) in new financing and strengthens leadership in the RNA interference (RNAi) therapeutics industry -

Alnylam Pharmaceuticals, Inc., and Ribopharma AG, the two leading companies in the field of therapeutic RNA interference (RNAi), announced today that they have merged. This strategic transaction creates an international company, with the leading position in the fundamental patents, technology, and know-how that underlie the discovery, development, and commercialization of RNAi-based therapeutics. Concurrent with the merger, the combined entity secured an additional $24.6 million (EUR 21.5 million) in private equity financing making it among the best capitalized companies in the field of RNAi-based therapeutics.

The company will have operating units in Cambridge, Massachusetts, and Kulmbach, Germany, each with specific responsibilities including RNAi research and development, and global headquarters in Cambridge, Massachusetts. Dr. John Maraganore, formerly president and CEO of Alnylam, will be president and CEO of the merged company. Under the merger agreement, which has been approved by the boards of directors of both companies, shareholders of Alnylam and Ribopharma will exchange their shares for shares in the merged entity.

The $24.6 million (EUR 21.5 million) in private equity financing includes investments by Polaris Venture Partners, Abingworth Management, Cardinal Partners, Atlas Venture, and ARCH Venture Partners. The funding will be used to accelerate the company's research and commercial initiatives in RNAi-based therapeutics, while expanding its commercial and scientific teams. With this financing, the company's total paid-in capital exceeds $43 million (EUR 37 million).

"We are positioned to be the leader in RNAi, one of the most exciting new areas of drug innovation seen in decades," said Dr. John Maraganore, president and CEO. "Our combined team, intellectual property portfolio, financial resources, and drug discovery and development capabilities position us to deliver on the promise of RNAi-based therapeutics to meet unmet medical needs for many important diseases."

The merger will result in increased competitive strengths and synergies across several key areas. In the area of intellectual property, the company will have a formidable worldwide intellectual property estate, which includes patents in the fundamental technology of RNAi from Alnylam and core patents relating to product composition and therapeutic applications of RNAi from Ribopharma. In addition, the company will have the foundation of a strong product-generating engine for RNAi therapeutics, based on the pioneering research and development programs of Alnylam and Ribopharma.

With capabilities in both North American and Europe, the company will continue to advance its strong collaborations with leading academic institutions in the field of RNAi, including the Massachusetts Institute of Technology, the Max Planck Institute, University of Massachusetts Medical Center and the Rockefeller University. Led by president and CEO Dr. John Maraganore, the company will have an experienced management team, including Roland Kreutzer, founder and previously CEO of Ribopharma who will now serve as chief operating officer of the Ribopharma operating unit, and Stefan Limmer, founder and previously chief science officer of Ribopharma who will now serve as chief technology officer of the combined entity, as well as other members from Alnylam's and Ribopharma's management teams.

"As a unified team, we can enhance and accelerate our research, drug discovery and product development of RNAi-based therapies, creating a powerful product-focused company," said Roland Kreutzer, chief operating officer of the Ribopharma operating unit. "Both companies have a shared commitment to the discovery and development of novel drugs and a shared passion to pioneer in the emerging field of RNAi."

The board of directors of the new company will consist of John Clarke, founder and chairman of the board of Alnylam and managing general partner of Cardinal Partners, Christoph Westphal, founder and vice chairman of the board of Alnylam and general partner of Polaris Venture Partners, John Berriman, director of Abingworth Management, Peter Barrett, senior principal of Atlas Venture, Phillip Sharp, Nobel Laureate and professor at MIT Center for Cancer Research, Paul Schimmel, professor at Scripps Research Institute, and John Maraganore, president and CEO of Alnylam.

About the Company The merger of Alnylam and Ribopharma creates Alnylam Holding Co., the leading company in the emerging field of RNA interference (RNAi) whose vision is to harness a revolution in biology for human healthTM. Growing from its foundation as the world's first company focused on RNAi-based therapeutics, the company is built around the leading capabilities of its two operating units, Alnylam Pharmaceuticals of Cambridge, Massachusetts, and Ribopharma of Kulmbach, Germany. Over the last several years, RNAi has been identified as a fundamental cellular mechanism for gene silencing. The company's leadership in the field of RNAi is supported by its preeminent founders and advisors and its strengths in fundamental patents, technology, and know-how that underlie the commercialization of RNAi-based therapeutics. The company's focus is to discover, develop, and commercialize therapeutic products based on RNAi for a broad range of therapeutic indications including viral, oncologic, metabolic, CNS and autoimmune diseases. The company's mission is to lead research in the field of RNAi, to build the leading pipeline of RNAi-based therapeutics, and to emerge as business leaders. Its global headquarters are in Cambridge, MA.