Discovery and delivery strategies for engineered live biotherapeutic products

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.

Automated summary

In this article, the authors discuss the emerging class of therapeutics called live biotherapeutic products (LBPs) which involve genetically engineered microbes. They describe the discovery and delivery strategies of LBPs using omics-based methods and highlight the challenges these therapeutics face in the gut microenvironment. The authors also propose an integrated approach to tailor and optimize LBP efficacy.