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Bridging the Gap: A Roadmap to Breaking the Biological Design Barrier

机译:缩小差距:打破生物设计障碍的路线图

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摘要

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.
机译:本文对生物工程中正在出现的瓶颈进行了分析,并指出了可以克服的瓶颈。近年来,大量的合成生物学工具得到了发展,主要分为两类:旨在从生物规格映射到实现这些规格的核酸序列的高级“设计”工具,以及低级的“构建和测试”工具这些工具旨在更快,更便宜,更可靠地制造这些序列,以及在工程生物中的行为测定。但是,这两个系列之间存在很大差距:我们仍然缺乏有效地确定设计阶段考虑的许多可能候选序列中的哪一个在构建时最有可能产生有用结果所需的预测模型和组件特征数据和测试。随着低级工具的不断成熟,生物系统工程的瓶颈正在转移,以设计为主导,从而使这一差距成为发展的关键障碍。考虑到如何解决这一差距,我们发现,广泛采用易于使用的分析和测定方法可能会导致可用的预测模型和组件表征模型的快速改进,最近的许多结果证明了这一点。反过来,这种有利的发展可能会允许高级工具突破设计障碍并支持转化性生物应用的快速发展。

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