An On/Off Swtich for Genes


By Jim Kozubek J. コズベック
English 日本語 日本語
Humans don’t molt,” R. J. Kirk tells me. Kirk is a billionaire geek who runs his offices out of West Palm Beach, Fla., a balmy land of pelicans and tangled mangroves. He built his fortune on conventional medications that can be taken as a pill, and I had phoned to talk about his newest en­­deavors in biotech. I wasn’t expecting to hear about bugs. But the molting process, in which a growing insect builds a new exoskeleton to replace an old one that no longer fits, turns out to have some very important properties that can be adapted to make gene therapy, still a largely experimental procedure, safer.  「人間は脱皮しない」。カーク(R. J. Kirk)は私にそう語った。彼はペリカンとマングローブ林で知られる温暖なフロリダ州ウェストパームビーチの外れで会社を経営する億万長者の変わり者だ。錠剤として服用する従来の薬剤によって富を築いた人物で,私が取材を申し込んだのはバイオテクノロジー分野での最新の取り組みについて話を聞くためだった。虫の話が出てくるとは予想外だったが,昆虫が成長に伴い身体に合わなくなった古い外骨格を新しいものに取り替える脱皮の過程には非常に重要な特性がいくつかあり,これらを応用すればいまだに実験的な手法である遺伝子治療をより安全なものにできるという。
Doctors would like to deliver copies of working genes to people to treat a variety of hereditary ills. Genes provide cells with the instructions for manufacturing proteins, among other things, and so inserting a functional gene into the body can, in theory, provide a lasting supply of whatever missing proteins a patient might need. But gene therapy has had a troubled history, in part because scientists cannot precisely control where a new gene inserts into a cell’s DNA and how active it is once there (which determines how much protein is produced). These problems can lead to unwanted side effects—including the development of malignant tumors.  様々な遺伝性疾患を治療する目的で,正常に機能する遺伝子を患者に導入するのが遺伝子治療だ。遺伝子はもっぱらタンパク質の生産を細胞に指示するものなので,正常な遺伝子を体内に導入すれば,理論的には,患者に欠けているどんなタンパク質でも継続して供給できる。
A logical solution to the problem of having proteins made in undesirable places and amounts would be to combine a therapeutic gene with a switch that could reliably turn it on or off as needed. As it happens, says Kirk—who is chairman and chief executive officer of Intrexon, a company that is developing new genetic engineering techniques—insects routinely use just such a switch to control molting.  タンパク質が作られる場所と量を制御できないという問題を解決するには,治療用遺伝子に“スイッチ”を取り付けて,必要に応じて活性を確実にオン・オフするのが合理的だろう。遺伝子工学の新技術開発に取り組むイントレキソン社の会長兼最高経営責任者であるカークによると,昆虫はまさにそのようなスイッチを使って脱皮をコントロールしている。
Here’s the thing. Insects do not just sort of molt, starting and then stopping partway; they either do it, or they don’t. The genetic pathway that drives the process must remain completely turned off until the time is right. The gene that interests Kirk serves as the master switch for all this activity. It codes for a hormone called ecdysone. As ecdysone surges through the insect, it turns on a raft of other genes to start building the new exoskeleton. After the new exoskeleton is ready, the insect discards the old one. Once molting is nearing completion, the levels of ecdysone fall to zero—at which point the genetic pathway turns off. More important, from Intrexon’s point of view, the switch is airtight when turned off—molting does not happen in the absence of ecdysone. The switch does not allow this group of genes to act together again until molting is set to begin.  これはもってこいだ。昆虫は中途半端な脱皮はしない。脱皮を始めて途中でやめることはなく,脱皮するかしないかだ。だから,このプロセスを動かしている遺伝子経路は時が来るまで完全にオフになっているはずだ。カークが注目した昆虫の遺伝子は,脱皮全体のマスタースイッチとして機能するもので,「エクジソン」というホルモンを作り出す。