Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
Nat Rev Microbiol. 2018 Apr;16(4):214-225. doi: 10.1038/nrmicro.2017.172. Epub 2018 Feb 5.
Our ability to generate bacterial strains with unique and increasingly complex functions has rapidly expanded in recent times. The capacity for DNA synthesis is increasing and costing less; new tools are being developed for fast, large-scale genetic manipulation; and more tested genetic parts are available for use, as is the knowledge of how to use them effectively. These advances promise to unlock an exciting array of 'smart' bacteria for clinical use but will also challenge scientists to better optimize preclinical testing regimes for early identification and validation of promising strains and strategies. Here, we review recent advances in the development and testing of engineered bacterial diagnostics and therapeutics. We highlight new technologies that will assist the development of more complex, robust and reliable engineered bacteria for future clinical applications, and we discuss approaches to more efficiently evaluate engineered strains throughout their preclinical development.
近年来，我们生成具有独特且日益复杂功能的细菌菌株的能力迅速提高。DNA 合成的能力不断增强，成本也越来越低；新的工具被开发出来用于快速、大规模的遗传操作；更多经过测试的遗传部件可供使用，并且我们也了解了如何有效地使用它们。这些进展有望为临床应用解锁一系列令人兴奋的“智能”细菌，但也将挑战科学家们，需要更好地优化临床前测试方案，以便及早识别和验证有前途的菌株和策略。在这里，我们回顾了工程细菌诊断和治疗的最新进展和测试。我们强调了新技术，这些新技术将有助于开发更复杂、更强大和更可靠的工程细菌，用于未来的临床应用，我们还讨论了在临床前开发过程中更有效地评估工程菌株的方法。
