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真核生物中基于规则的合成转录因子设计

Rule-based design of synthetic transcription factors in eukaryotes.

作者信息

Purcell Oliver, Peccoud Jean, Lu Timothy K

机构信息

Department of Electrical Engineering & Computer Science and Department of Biological Engineering, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States of America.

出版信息

ACS Synth Biol. 2014 Oct 17;3(10):737-44. doi: 10.1021/sb400134k. Epub 2014 Jan 3.

DOI:10.1021/sb400134k
PMID:24933274
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4097980/
Abstract

To design and build living systems, synthetic biologists have at their disposal an increasingly large library of naturally derived and synthetic parts. These parts must be combined together in particular orders, orientations, and spacings to achieve desired functionalities. These structural constraints can be viewed as grammatical rules describing how to assemble parts together into larger functional units. Here, we develop a grammar for the design of synthetic transcription factors (sTFs) in eukaryotic cells and implement it within GenoCAD, a Computer-Aided Design (CAD) software for synthetic biology. Knowledge derived from experimental evidence was captured in this grammar to guide the user to create designer transcription factors that should operate as intended. The grammar can be easily updated and refined as our experience with using sTFs in different contexts increases. In combination with grammars that define other synthetic systems, we anticipate that this work will enable the more reliable, efficient, and automated design of synthetic cells with rich functionalities.

摘要

为了设计和构建生命系统,合成生物学家可以利用越来越多的天然衍生和合成部件库。这些部件必须按照特定的顺序、方向和间距组合在一起,以实现所需的功能。这些结构限制可以被视为描述如何将部件组装成更大功能单元的语法规则。在这里,我们开发了一种用于真核细胞中合成转录因子(sTF)设计的语法,并在GenoCAD(一种用于合成生物学的计算机辅助设计(CAD)软件)中实现了它。从实验证据中获得的知识被纳入这个语法中,以指导用户创建应按预期运行的定制转录因子。随着我们在不同背景下使用sTF的经验增加,该语法可以很容易地更新和完善。结合定义其他合成系统的语法,我们预计这项工作将实现具有丰富功能的合成细胞更可靠、高效和自动化的设计。

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