Engineered microbial systems for advanced drug delivery

Haosheng Shen; Nikhil Aggarwal; Kwok Soon Wun; Yung Seng Lee; In Young Hwang; Matthew Wook Chang

doi:10.1016/j.addr.2022.114364

Engineered microbial systems for advanced drug delivery

Adv Drug Deliv Rev. 2022 Aug:187:114364. doi: 10.1016/j.addr.2022.114364. Epub 2022 May 30.

Authors

Haosheng Shen¹, Nikhil Aggarwal¹, Kwok Soon Wun², Yung Seng Lee³, In Young Hwang⁴, Matthew Wook Chang⁵

Affiliations

¹ NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore; Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
² NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore; Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
³ NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore; Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁴ NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore; Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: inyoung_hwang@nus.edu.sg.
⁵ NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore; Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: bchcmw@nus.edu.sg.

PMID: 35654214
DOI: 10.1016/j.addr.2022.114364

Abstract

The human body is a natural habitat for a multitude of microorganisms, with bacteria being the major constituent of the microbiota. These bacteria colonize discrete anatomical locations that provide suitable conditions for their survival. Many bacterial species, both symbiotic and pathogenic, interact with the host via biochemical signaling. Based on these attributes, commensal and attenuated pathogenic bacteria have been engineered to deliver therapeutic molecules to target specific diseases. Recent advances in synthetic biology have enabled us to perform complex genetic modifications in live bacteria and bacteria-derived particles, which simulate micron or submicron lipid-based vectors, for the targeted delivery of therapeutic agents. In this review, we highlight various examples of engineered bacteria or bacteria-derived particles that encapsulate, secrete, or surface-display therapeutic molecules for the treatment or prevention of various diseases. The review highlights recent studies on (i) the production of therapeutics by microbial cell factories, (ii) disease-triggered release of therapeutics by sense and respond systems, (iii) bacteria targeting tumor hypoxia, and (iv) bacteria-derived particles as chassis for drug delivery. In addition, we discuss the potential of such drug delivery systems to be translated into clinical therapies.

Keywords: Bacteria-derived particles; Microbial cell factories; Microbial drug delivery; Microbial sensors; Synthetic biology.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Bacteria / genetics
Drug Delivery Systems
Humans
Microbiota*
Synthetic Biology*