Engineered Escherichia coli as a microbial cell factory for intracellular protein delivery: strains, vectors, mechanisms, and therapeutic applications

Escherichia coli (E. coli) has emerged as a promising vector of therapeutic proteins into target cells due to its high fidelity to genetic manipulations, short generation times, and well-known molecular pathways. Over the years, the use of E. coli as a delivery vector has been explored in various mechanisms. This review aims to discuss the mechanisms through which E. coli can express and transport therapeutic proteins to target cells. Various delivery systems have been developed using E. coli, starting from the simple plasmid vectors, to outer membrane vesicles and, in some cases, live bacteria itself which can transport proteins into cells. These E. coli based systems are of immense potential in targeted drug delivery and therapeutic applications and have made E. coli to lead in novel biotechnological developments. However, there are still many challenges, concerning the improvement of the safety and efficacy of E. coli for protein delivery into cells, especially in regards to delivery efficiency and directional control in a real biological environment. Most of these challenges have been solved by the recent developments in synthetic biology, genetic engineering and E. coli is gradually becoming a versatile vector for protein therapeutic delivery into cells.