Engineering of bacterial outer membrane vesicles for biotechnological applications

Outer membrane vesicles (OMVs) are spherical, nano-sized proteoliposomes naturally secreted by Gram-negative bacteria. By incorporating parental membrane components and encapsulating diverse cellular cargos, OMVs function as potent mediators of biological communication. Despite inherent challenges, including low production yields, heterogeneous composition, and stochastic cargo loading, OMVs hold immense promise across broad biotechnological landscapes. In this review, we examine current advancements in OMV chassis engineering and functional diversification, providing a comprehensive synthetic biology perspective on their role as modular and programmable systems. We discuss five established strategies for inducing hyper-vesiculation alongside two complementary frameworks for constructing synthetic vesicles. These engineered OMVs facilitate transformative applications spanning biomedical and biotechnological domains, notably as high-fidelity platforms for studying membrane proteins within their native lipid environments. As synthetic biology increasingly converge with materials science, future innovations such as stimuli-responsive vesicles, self-assembling architectures, and hybrid bio-synthetic materials are poised to emerge. Such advancements position synthetic OMVs at a critical intersection to address complex challenges in medicine, environmental remediation, and advanced materials science, offering unprecedented opportunities for both fundamental discovery and industrial applications.