Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia.
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Appl Microbiol Biotechnol. 2019 Mar;103(5):2053-2066. doi: 10.1007/s00253-019-09628-y. Epub 2019 Jan 17.
Lactic acid bacteria (LAB) have a long-term history of use in food industry and are becoming attractive for use in therapy on account of their safety, intrinsic beneficial health effects, and considerable biotechnological potential. The established systems for engineering are combined with novel approaches, such as CRISPR-Cas, to enable the use of LAB as vectors for delivery of various therapeutic molecules. The latter are either secreted or surface displayed and can be used for the treatment or prevention of numerous conditions: inflammatory bowel diseases, infections, autoimmune diseases, and even cancer. This review presents some recent data on engineering of LAB, with the emphasis on the most commonly used genera Lactococcus and Lactobacillus. Their use for the delivery of therapeutic proteins is discussed, while a special focus is given to the delivery of therapeutic peptides. Therapeutically relevant improvements of engineered LAB, such as containment systems, ability to visualize bacteria, or target specific host cells are also addressed. Future engineering of LAB for therapy will adopt the capabilities of synthetic biology, with first examples already emerging.
乳酸菌（LAB）在食品工业中的应用历史悠久，由于其安全性、内在的有益健康作用以及相当大的生物技术潜力，它们开始吸引人们用于治疗用途。现有的工程系统与新型方法（如 CRISPR-Cas）相结合，使 LAB 能够用作递送各种治疗分子的载体。这些分子可以分泌或表面展示，并可用于治疗或预防多种疾病：炎症性肠病、感染、自身免疫性疾病，甚至癌症。本文综述了乳酸菌工程的一些最新数据，重点介绍了最常用的乳球菌属和乳杆菌属。讨论了它们在递送治疗性蛋白质中的应用，特别关注治疗性肽的递送。还讨论了工程化 LAB 在治疗中的相关改进，例如包含系统、可视化细菌的能力或靶向特定宿主细胞的能力。未来的 LAB 治疗工程将采用合成生物学的能力，已经出现了第一个例子。
