Raytheon BBN Technologies , Cambridge, MA , USA.
Front Bioeng Biotechnol. 2015 Jan 20;2:87. doi: 10.3389/fbioe.2014.00087. eCollection 2014.
This paper presents an analysis of an emerging bottleneck in organism engineering, and paths by which it may be overcome. Recent years have seen the development of a profusion of synthetic biology tools, largely falling into two categories: high-level "design" tools aimed at mapping from organism specifications to nucleic acid sequences implementing those specifications, and low-level "build and test" tools aimed at faster, cheaper, and more reliable fabrication of those sequences and assays of their behavior in engineered biological organisms. Between the two families, however, there is a major gap: we still largely lack the predictive models and component characterization data required to effectively determine which of the many possible candidate sequences considered in the design phase are the most likely to produce useful results when built and tested. As low-level tools continue to mature, the bottleneck in biological systems engineering is shifting to be dominated by design, making this gap a critical barrier to progress. Considering how to address this gap, we find that widespread adoption of readily available analytic and assay methods is likely to lead to rapid improvement in available predictive models and component characterization models, as evidenced by a number of recent results. Such an enabling development is, in turn, likely to allow high-level tools to break the design barrier and support rapid development of transformative biological applications.
本文分析了生物工程中一个新出现的瓶颈，并探讨了可能的突破途径。近年来，大量的合成生物学工具得到了发展，这些工具主要分为两类：一类是高级的“设计”工具，旨在将生物规格映射到实现这些规格的核酸序列上；另一类是低级的“构建和测试”工具，旨在更快、更便宜、更可靠地构建这些序列，并测试它们在工程生物中的行为。然而，这两类工具之间存在一个主要的差距：我们仍然缺乏有效的预测模型和组件特征数据，无法准确判断在设计阶段考虑的众多候选序列中，哪些序列最有可能在构建和测试时产生有用的结果。随着低级工具的不断成熟，生物系统工程的瓶颈正在向设计主导型转变，这使得这一差距成为阻碍进展的关键障碍。在考虑如何解决这一差距时，我们发现广泛采用现成的分析和检测方法，可能会导致可用的预测模型和组件特征模型迅速改进，这一点从最近的一些成果中就可以得到证明。这种促进发展的方法反过来又可能使高级工具突破设计瓶颈，支持具有变革性的生物应用的快速发展。
