Genetically engineered outer membrane vesicles as next-generation bionanomaterials for therapeutic and diagnostic...

Outer membrane vesicles (OMVs), naturally released by Gram-negative bacteria, represent a unique class of bionanomaterials with inherent immunogenicity, efficient cellular delivery, and scalable production. However, their native toxicity, compositional heterogeneity, and lack of targeting specificity have hindered broader therapeutic translation. Advances in genetic engineering and synthetic biology have revolutionized OMV design, transforming these biological byproducts into highly programmable bionanomaterial platforms. This review systematically outlines the key engineering strategies for OMVs, including surface display for targeting and immunomodulation, cargo loading for encapsulating nucleic acids, proteins, and drugs, and membrane modulation for tuning stability and safety. We highlight the transformative applications of genetically engineered OMVs (geOMVs) in cancer immunotherapy, next-generation vaccines, targeted delivery, and diagnostic imaging. Finally, we discuss the critical challenges in the clinical translation-such as scalable manufacturing, safety profiling, and regulatory pathways-and propose future directions integrating synthetic biology, materials science, and artificial intelligence to realize the full potential of geOMVs as intelligent, precision therapeutic and diagnostic platforms.