Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zurich, Basel, Switzerland.
Science. 2011 Jun 24;332(6037):1565-8. doi: 10.1126/science.1203535.
Synthetic biology has advanced the design of genetic devices that can be used to reprogram metabolic activities in mammalian cells. By functionally linking the signal transduction of melanopsin to the control circuit of the nuclear factor of activated T cells, we have designed a synthetic signaling cascade enabling light-inducible transgene expression in different cell lines grown in culture or bioreactors or implanted into mice. In animals harboring intraperitoneal hollow-fiber or subcutaneous implants containing light-inducible transgenic cells, the serum levels of the human glycoprotein secreted alkaline phosphatase could be remote-controlled with fiber optics or transdermally regulated through direct illumination. Light-controlled expression of the glucagon-like peptide 1 was able to attenuate glycemic excursions in type II diabetic mice. Synthetic light-pulse-transcription converters may have applications in therapeutics and protein expression technology.
合成生物学已经推动了遗传装置的设计，可以用于重新编程哺乳动物细胞中的代谢活动。通过将黑视蛋白的信号转导功能与激活 T 细胞核因子的控制回路相连接，我们设计了一种合成信号级联系统，使不同细胞系在培养或生物反应器中生长或植入小鼠后，能够实现光诱导的转基因表达。在体内携带包含光诱导转基因细胞的腹腔内中空纤维或皮下植入物的动物中，可以通过光纤远程控制血清中人糖蛋白分泌型碱性磷酸酶的水平，或通过直接照射进行经皮调节。光控表达胰高血糖素样肽 1 能够减轻 2 型糖尿病小鼠的血糖波动。合成光脉冲转录转换器可能在治疗和蛋白质表达技术中有应用。
