Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, USA.
Trends Biotechnol. 2022 Mar;40(3):354-369. doi: 10.1016/j.tibtech.2021.08.002. Epub 2021 Sep 1.
Genetically engineered microbes that secrete therapeutics, sense and respond to external environments, and/or target specific sites in the gut fall under an emergent class of therapeutics, called live biotherapeutic products (LBPs). As live organisms that require symbiotic host interactions, LBPs offer unique therapeutic opportunities, but also face distinct challenges in the gut microenvironment. In this review, we describe recent approaches (often demonstrated using traditional probiotic microorganisms) to discover LBP chassis and genetic parts utilizing omics-based methods and highlight LBP delivery strategies, with a focus on addressing physiological challenges that LBPs encounter after oral administration. Finally, we share our perspective on the opportunity to apply an integrated approach, wherein discovery and delivery strategies are utilized synergistically, towards tailoring and optimizing LBP efficacy.
基因工程微生物分泌治疗剂，感知和响应外部环境，和/或靶向肠道中的特定部位，属于一类新兴的治疗剂，称为活体生物治疗产品（LBPs）。作为需要共生宿主相互作用的活体生物，LBPs 提供了独特的治疗机会，但在肠道微环境中也面临着明显的挑战。在这篇综述中，我们描述了最近的方法（通常使用传统的益生菌微生物来展示），利用基于组学的方法来发现 LBP 底盘和遗传元件，并强调了 LBP 传递策略，重点是解决 LBPs 口服后遇到的生理挑战。最后，我们分享了我们的观点，即有机会应用综合方法，其中发现和传递策略协同利用，以定制和优化 LBP 的疗效。
