Advancement of Engineered Bacteria for Orally Delivered Therapeutics

Abstract

The use of bacteria and their biotic components as therapeutics has shown great potential in the treatment of diseases. Orally delivered bacteria improve patient compliance compared with injection‐administered bacteria and are considered the preferred mode. However, due to the harsh gastrointestinal environment, the viability and therapeutic efficacy of orally delivered bacteria are significantly reduced in vivo. In recent years, with the rapid development of synthetic biology and nanotechnology, bacteria and biotic components have been engineered to achieve directed genetic reprogramming for construction and precise spatiotemporal control in the gastrointestinal tract, which can improve viability and therapeutic efficiency. Herein, a state‐of‐the‐art review on the current progress of engineered bacterial systems for oral delivery is provided. The different types of bacterial and biotic components for oral administration are first summarized. The engineering strategies of these bacteria and biotic components and their treatment of diseases are next systematically summarized. Finally, the current challenges and prospects of these bacterial therapeutics are highlighted that will contribute to the development of next‐generation orally delivered bacteriotherapy.

Genetically engineered bacteria: a new frontier in targeted drug delivery

“…37 Due to their capacity to promote mucosal immunity, bacterial ghosts-based vaccines have been demonstrated to be an effective technique for H. pylori immunization as they transmit highly conserved antigens to the stomach mucosa. 38 In this context, researchers demonstrated that oral vaccination of modified bacterial ghosts with H. pylori -infected C57BL/6 mice could produce potent anti- H. pylori antibody titers, which resulted in not only considerable eradication of infection but also decrease in bacterial colonization in the infected animals. 39…”

Advanced Bioinspired Multifunctional Platforms Focusing on Gut Microbiota Regulation

“…The negative charge 296 and various substances with specific functional groups, such as peptidoglycan, 297 lipids, 298 and proteins on the bacterial surface provide sites for surface modification, which can aid in enhancing the functionality of probiotics via electrostatic/hydrophobic interactions, covalent coupling, bio-orthogonal reactions, membrane encapsulation, and genetic engineering. 299 Similar to microencapsulation, surface modification represents a strategy to improve the delivery of oral probiotics to the gastrointestinal tract, thereby maintaining their functionality during transit through the gut and enhancing their availability for absorption. In a study, dioleoylphosphatidic acid (DOPA) and cholesterol were utilized to coat EcN bacteria in a calcium phosphate buffer via biointerfacial supramolecular self-assembly.…”

“…Therefore, surface coating or modification is a promising means of addressing the shortcomings of probiotic delivery systems. The negative charge and various substances with specific functional groups, such as peptidoglycan, lipids, and proteins on the bacterial surface provide sites for surface modification, which can aid in enhancing the functionality of probiotics via electrostatic/hydrophobic interactions, covalent coupling, bio-orthogonal reactions, membrane encapsulation, and genetic engineering …”