Genetic principles enabling the creation of bacteria-based therapeutics

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Publication Details

Journal
Genetics
Published
2026-09-17
DOI
https://doi.org/10.1093/genetics/iyag235
Primary Topic
Cancer Research and Treatments
Type
article
Field-Weighted Citation Impact
0.00

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article

Genetic principles enabling the creation of bacteria-based therapeutics

Thomas M. Groseclose, Ashley B. Williams, Lyndsey Linke, Darcy S O Mora et al.
Genetics
Cancer Research and Treatments
article

Genetic principles enabling the creation of bacteria-based therapeutics

Thomas M. Groseclose, Ashley B. Williams, Lyndsey Linke, Darcy S O Mora, Sara A M Holec, Darrian Newman
article en

Abstract

Genetic engineering can transform bacteria (including Salmonella, Escherichia coli, Listeria, and Yersinia) from naturally occurring microbes into programmable therapeutics. Unlike passive platforms, engineered bacteria can localize to defined biological niches, sense environmental cues, regulate programmed activity in situ, interact with host tissues in novel ways, and persist for controlled periods. These properties make bacteria versatile medicines but require genetic control of precision, safety, stability, and activity under clinical conditions. Major design layers include strain or "chassis" selection, attenuation and biocontainment, control of therapeutic activity, targeting and persistence, and genotype-to-phenotype stability during manufacturing and in vivo use. These features also create liabilities, including off-target behavior, unstable expression, and evolutionary loss of function under selection. Progress depends on safe, clinically translatable chassis with integrated, bounded, and durable behaviors. This review examines the genetic design principles and liabilities of bacteria-based therapeutics, approaches used to produce clinical and near-clinical candidates, and the emergence of programmed bacteria delivering complete gene editing systems to therapeutically relevant cells.

Genetics
Kai Biotech (South Korea) (KR)
National Institutes of Health, National Institute of Allergy and Infectious Diseases
Responsible consumption and production
Openalex Percentile: Top 16%
Cancer Research and Treatments
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