Synthetic Microbes As Drug Delivery Systems

Abstract

Synthetic cell therapy is a field that has broad potential for future applications in human disease treatment. Next generation therapies will consist of engineered bacterial strains capable of diagnosing disease, producing and delivering therapeutics, and controlling their numbers to meet containment and safety concerns. A thorough understanding of the microbial ecology of the human body and the interaction of the microbes with the immune system will benefit the choice of an appropriate chassis that engrafts stably and interacts productively with the resident community in specific body niches.

Programming a Human Commensal Bacterium, Bacteroides thetaiotaomicron, to Sense and Respond to Stimuli in the Murine Gut Microbiota

“…For example, our constitutive and inducible systems, integrases, and CRISPRi regulators could be integrated for higher-order computation in B. thetaiotaomicron , such as digital logic, memory, and analog circuits. These engineered commensals could be used to map the dose-dependent and temporal effects of specific surface polysaccharides (Liu et al, 2008) or heterologous pathways (Claesen and Fischbach, 2015) on colonization and maintenance of the gut microbiota and on host health. Higher-order combinations of inducible promoters linked with integrases could achieve Boolean logic with embedded cellular memory (Siuti et al, 2013), enabling surveillance of the gut environment.…”

Acoustic reporter genes for noninvasive imaging of microorganisms in mammalian hosts

“…The E. coli strain Nissle 1917 (EcN) is a probiotic microbe capable of colonizing the mammalian GI tract 25 . EcN has been used clinically in humans for 100 years to treat enteric infection and inflammatory bowel conditions 25 , and is a common chassis for therapeutic synthetic biology 3,5,6,26 . EcN cells transformed with a plasmid expressing ARG1 produced abundant gas vesicles (Fig.…”

Fabrication of nanocomposites and hybrid materials using microbial biotemplates

“…For example, bioengineers have been designing various engineered bacteria to perform different specialized functions, such as detection and diagnosis of diseases [75] and production of therapeutics [76] and their delivering [77], which can self-eliminate after therapy [78]. With the development of synthetic biology, the future directions of bacterial cell therapy systems will set a variety of abilities in one and will be smarter as autonomous microbial Bphysicians^ [79].…”