Genetically engineered bacterium: Principles, practices, and prospects

Abstract

Advances in synthetic biology and the clinical application of bacteriotherapy enable the use of genetically engineered bacteria (GEB) to combat various diseases. GEB act as a small ‘machine factory’ in the intestine or other tissues to continuously produce heterologous proteins or molecular compounds and, thus, diagnose or cure disease or work as an adjuvant reagent for disease treatment by regulating the immune system. Although the achievements of GEBs in the treatment or adjuvant therapy of diseases are promising, the practical implementation of this new therapeutic modality remains a grand challenge, especially at the initial stage. In this review, we introduce the development of GEBs and their advantages in disease management, summarize the latest research advances in microbial genetic techniques, and discuss their administration routes, performance indicators and the limitations of GEBs used as platforms for disease management. We also present several examples of GEB applications in the treatment of cancers and metabolic diseases and further highlight their great potential for clinical application in the near future.

Genetically engineered bacteria: a new frontier in targeted drug delivery

“…33 So far, the routes of GEB administration have primarily consisted of oral, intravenous, intratumoral, and nasal methods. 34 In what follows, we have focused on GEB administration methods as well as their application in the treatment of cancer and intestinal disorders.…”

Engineering bacteria to modulate host metabolism

“…This is of particular interest as the production of a certain molecule or enzyme can be triggered only when needed. Nevertheless, even with the development of such a wide range of techniques, it is still challenging to create an engineered microorganism as most chassis will inactivate the expression of foreign genes 14 . Probiotic microorganisms such as Lactobacillus spp.…”

Editorial: Microorganisms and their derivatives for cancer therapy

“…Cancer remains an unsolved and challenging problem. In 1890, Dr. William Bradley Coley attempted to use a mixture of dead microbes to treat cancers (Dobosz and Dzieciatkowski, 2019;Liu et al, 2022), establishing the foundation of bacteria-mediated cancer therapy. Given the recent advances in the study of the human microbiome that revealed its crucial role in tumorigenesis, development, therapy, and prognostic evaluation, additional research efforts on cancer microbial therapies have been conducted (Kurtz et al, 2019;Feng et al, 2022), with new findings supporting the potential role of bacteriolytic therapy in cancer.…”

“…Encouragingly, dozens of clinical trials using CpG DNA in various cancers are being conducted (Ma et al, 2018). Recently, given the advances on DNA sequencing, genetic operation and microorganism culture techniques, especially the heterogeneous expression of large gene clusters from non-culturable microbes, several functional substances that greatly contribute to drug libraries of anticancer agents and antibacteria have been successfully produced (Liu et al, 2022). In Zhang's work, the cell-free culture supernatant of Lactiplantibacillus plantarum YT013 isolated from serofluid dish showed remarkable inhibition of different tumors, suggesting Lactiplantibacillus plantarum YT013 as a good candidate for anticancer therapies.…”

“…Extracts from Lactipantibacillus plantarum YT013 further enriched the anticancer drug library, given that the effective compounds can be identified and analyzed clearly. Several well-known bacteria, including Salmonella typhimurium, Escherichia coli Nissle 1917, Clostridium difficile, Listeria monocytogenes, and Bifidobacterium have been widely used as tumor-targeting bacteria (Liu et al, 2022). However, additional new tumor-targeting bacterium could not be easily found from millions of published papers.…”