Discovery and delivery strategies for engineered live biotherapeutic products.

Mairead K Heavey, Deniz Durmusoglu, Nathan Crook, Aaron C Anselmo

Journal: Trends in biotechnology 2022;40(3):354-369

PMID: 34481657

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Abstract

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.

Address: 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.; Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, USA. Electronic address: [email protected].; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: [email protected].

DOI: 10.1016/j.tibtech.2021.08.002

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MeSH Terms: Administration, Oral, Genetic Engineering, Probiotics