Advances in biocontainment strategies of engineered microbes for use in humans.

Genetically engineered microorganisms have been designed for use in many aspects of medicine. Advances in synthetic biology allow for the design of these organisms for a wide number of uses in a variety of environments. However, these advances are accompanied by the need for robust biocontainment strategies to prevent unwanted colonization and dissemination of engineered microorganisms. In this review, we discuss the current state of biocontainment strategies for use in biomedical applications. Many biocontainment strategies exist, including toxin-antitoxin systems, kill switches, auxotrophy, CRISPR-based targeted DNA degradation, nonstandard amino acids, and physical barriers. We discuss the use and caveats of these strategies both alone and in combination with each other. Additionally, we discuss the use and efficacy of these strategies in clinical trials. Finally, we discuss the need for standardized testing of containment escape. As use of these engineered microorganisms progresses, it is paramount that containment strategies advance with them to ensure safety, minimize environmental impact, and maintain a positive public view of this important work.