Black Joshua B, Perez-Pinera Pablo, Gersbach Charles A
Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708; email:
Center for Genomic and Computational Biology, Duke University, Durham, North Carolina 27708.
Annu Rev Biomed Eng. 2017 Jun 21;19:249-277. doi: 10.1146/annurev-bioeng-071516-044649.
The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.
将新功能编程到哺乳动物细胞中在研究和医学领域有着巨大的应用价值。DNA测序和合成能力的持续提升，迅速增进了我们在全基因组范围内对基因功能和调控机制的理解，同时也扩充了可用于编程细胞生物学的遗传元件库。新型研究工具的发明，包括如CRISPR/Cas9这类可靶向的DNA结合系统，以及能够识别并响应各种化学、机械和光学输入的传感-驱动装置，使得以前所未有的时空分辨率精确控制复杂的细胞行为成为可能。这些工具对于将合成生物学技术从原核生物和低等真核生物宿主扩展到哺乳动物系统至关重要。基因组和表观基因组编辑工具开发以及具有可编程遗传电路的设计细胞工程方面的最新进展，正在拓展预防、诊断和治疗疾病的方法，并为下一代药物建立个性化的治疗诊断策略。本综述总结了这些使能技术的发展及其在将哺乳动物合成生物学转变为研究和医学领域一个独特分支方面的应用。
