“Intelligent live bacteria robot” provides new strategies for in vivo diagnosis and treatment

Recently, the team of Professor Ye Bangce of the School of Bioengineering and State Key Laboratory of Bioreactors of East China University of Science and Technology published a paper in the international academic journal “Cell Host and Microorganism”, reporting on the design of intelligent engineered bacteria based on synthetic biology and the new strategy of integrating diagnosis and treatment of inflammatory bowel disease.


Intelligent microbial robot Photo courtesy of interviewee

“The system enables non-invasive real-time monitoring and recording of the occurrence and progression of inflammatory bowel disease in vivo, and alleviates the disease with a self-regulated delivery mode.” Ye Bangce said that with the rapid development of synthetic biology, the use of engineering methods through component development and gene circuit reprogramming and other means to build an “intelligent live bacteria robot” with the ability to diagnose diseases or target treatment diseases, which can sense disease signals in the human environment in real time and regulate downstream gene circuits to achieve the integrated functions of perception, conduction, calculation and feedback.

These micro “live bacteria robots” provide new opportunities and unique strategies for the diagnosis and treatment of various diseases, and with the continuous progress of science and technology, it is expected to form a set of systematic and controllable bacterial control loops, and through precise design and module construction, “intelligent live bacteria” will develop in a more targeted and safe direction, accelerating its transformation and application in clinical practice.

Inflammatory bowel disease (IBD) is the most common chronic inflammatory disease of the gastrointestinal tract. The incidence of IBD in China has increased sharply in recent decades, and if early diagnosis and treatment are not carried out, it is easy to increase the risk of depression, colorectal cancer and even death. Traditional diagnostic methods rely on invasive detection methods such as colonoscopy, which cause great pain to patients, and more importantly, it is difficult to achieve early diagnosis, and traditional treatment methods are difficult to control accurate drug dosages, resulting in side effects of drug overdose.

Based on this, the researchers developed an engineered smart probiotic i-ROBOT. The engineered bacterial system integrates 3 modules (fluorescence reporter, base editing recording module, and drug expression secretion module) to simultaneously perform the functions of diagnosing, recording and improving IBD in vivo. i-ROBOT can sense the emergence of intestinal disease molecular events (e.g., inflammatory markers thiosulfate) by generating an immediate fluorescence signal to reflect the current disease state, and the molecular recording system converts disease information into permanent single nucleotide mutations in genomic DNA, further leading to translational activation of functional proteins (e.g., chromogenic enzyme LacZ) that read inflammatory messages through DNA sequencing or visual color responses, which are long-term heritable. In addition, i-ROBOT has a self-regulating drug expression and secretion system that releases the appropriate concentration of therapeutic drugs according to the level of disease markers, without taking additional inducers, and this strategy effectively improves disease activity without causing side effects of overdose, such as intestinal fibrosis.


Illustration of intelligent engineering bacteria diagnosis and treatment of inflammatory marker response Photo courtesy of interviewee

i-ROBOT senses disease markers with high sensitivity and generates instant fluorescence signals, long-term recording signals, and self-regulatory responses such as expression and release of therapeutic proteins. This study provides novel strategies and proof-of-concepts for designing and customizing intelligent engineered bacteria for the integration of disease diagnosis and treatment. It is believed that in the near future, the application of microbial-based “intelligent live bacteria robot” in the medical field will become more and more diversified. (Source: China Science News, Zhang Shuanghu, Huang Xin)

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