Abstract:Microalgae, with the ability to harness solar energy to fix CO2 and convert it into organic compounds, have emerged as promising green cell factories. With the rapid development of cutting-edge biotechnologies, the research and application of photosynthetic microalgae have been expanding, leading to comprehensive and in-depth engineering of microalgae. The synthetic biology and genome editing technologies have enabled the applications of microalgae in medicine, agriculture, food, energy, and the environment. However, the survival and spreading of engineered microalgae in the natural environment pose potential safety risks to ecosystems and human health. To curb the risks caused by the spreading of engineered microalgae in the environment, biosafety policies should be formulated for engineered microalgae and the prevention and control technologies should be developed. Toward this goal, researchers have developed biocontainment systems, including positive strategies such as the design of toxic protein-based kill switches and passive strategies such as knocking out essential genes to construct the strains with nutritional deficiencies, thereby spatially containing engineered microalgae. This article summarizes the application of cutting-edge biotechnologies in the engineering of microalgae, the biosafety risks and management regulations associated with the escape of engineered microalgae, and the progress in novel biocontainment technologies established for engineered microalgae. Finally, this article gives insights into the future development direction of microalgae biocontainment.