- Human Pratices
In the previous research, we focused on Inflammatory Bowel Disease (IBD) from the video bloggers of bilibili (i.e., YouTube in China). These young patients claimed that the disease had seriously affected their lives. We went to the hospital to learn about the disease. With the consent of the patient and the hospital, we interviewed an IBD patient. We have learned that IBD is a chronic, non-specific inflammatory reaction mainly manifested in the intestinal mucosa. It is prone to repeated attacks and even has a potential cancer risk with a long onset cycle. The existing conventional therapies cannot wholly cure IBD, and even some drugs such as glucocorticoids have apparent side effects. Biological preparations like infliximab are costly, and many patients cannot afford the expense. In addition, the patients' diets are strictly controlled. When suffering from physical pain such as abdominal pain and diarrhoea, they are also under great mental stress caused by stigma.
At present, more than 10 million people worldwide suffer from IBD and related diseases, and the number of patients will gradually increase in the future. IBD has attracted more and more attention from all walks of life. We believe it is significant to fight for a better life for these tens of millions of people. We are concerned about IBD caused by intestinal flora disorders and hope to develop an engineered bacterial adjuvant to relieve patient's discomfort during the recovery period to improve their quality of life or treat patients who do not respond to conventional therapies.
The core concept of synthetic biology fits very well with the cocktail therapy we advocate. We hope to modularize our therapeutic elements, with particular emphasis on the interchangeability of promoters and open reading frames, allowing us to change the therapeutic genes of our choice and their expression methods at will. We finally hope to realize the transformation of E.coli Nissle 1917 and Lactococcus lactis, and choose four therapeutic factors to form our therapeutic elements.
Our four therapeutic genes come from different factors. Heterogeneous expression thioesterase from Bacteroides polymorpha can produce butyric acid，which can promote the repair of intestinal epithelial cells. Heterogeneous expression of human antimicrobial peptide LL37 to reduce the harm of endotoxin to the human body. Heterogeneous expression of superoxide dismutase can help clean up excessive active oxygen metabolites in the affected area. Heterogeneous expression of bile salt hydrolase can reverse the impairment of bile acid metabolism in the patient's intestine due to insufficient microbial bile salt hydrolase activity.
In order to fit the patient's situation, we used acid-responsive promoters to express these genes efficiently. We will match the treatment proportions of the four factors according to each patient's situation, personalize our engineered bacteria ratio, and truly achieve precise treatment from multiple angles and multiple factors.
We also used heat shock proteins and triclosan resistance genes to replace the routine antibiotic screening, making our products safer and designed a suicide switch to prevent engineered bacteria from escaping into the natural environment and into the blood.
In addition to paying attention to the demand for patient's health, we will also regularly collect stool samples from patients, perform metagenomic sequencing analysis on them, and follow up on the patient's intestinal flora and their health in real-time, thereby customizing the ratio of adjuvant strains. Aiming at the patient's strict diet and lifestyle, we hope to launch an online instant diet management platform that combines the results of the patient's fecal sequencing and daily diet records for analysis to solve the patient's difficulty in "what to eat? How to eat? What not to eat?". We can also use this platform to provide patients with scientific and target dietary guidance and encourage patients to return to everyday life. In response to the psychological distress that patients may have, we have built a "community" that allows users to communicate with each other, and we also hope that experts can be brought in for guidance. On this basis, we hope to integrate all the above parts and build an integrated online health management platform for users to use.
Considering the real needs of patients, we designed and optimized a series of hardware products to realize our personalized, customized services and drug delivery measures. We have designed a stool sampling kit suitable for long-term use by IBD patients, which overcomes the problems of existing devices such as the inability to collect loose stools and improper collection devices. At the same time, to improve patient medication compliance, protect patient privacy, and maintain the stability of live bacteria drugs, we have selected enteric-coated capsules to embed vacuum freeze-dried bacteria powder as our method of administration. In the end, we gathered all the products into one set, and designed a sample storage tube with a unique number and strong concealment for each patient, and fully considered the patient from the perspective of humanistic care.
Finally, to realize the value of our ideas, we conducted detailed market research and wrote a business plan. We hope that all disease-causing targets of IBD will be included in the platform's R&D pipeline, so that IBD patients can "survive with disease" in the same place as healthy people.
In the end, we put forward the concept of "treatment closed loop". We can track every patient who uses our products and cooperate with hospitals, biopharmaceutical factories, and bioinformatics analysis companies to promptly track and judge their health status and provide them with the most realistic probiotic drugs.
Specifically, we plan to provide patients and hospitals with our self-developed stool collection device so that they can collect samples. For these samples, we will perform metagenomic sequencing to analyze the patient's intestinal flora composition. We will also use qPCR technology to analyze the dynamic changes of the patient's intestinal flora and use the relative abundance analysis method to present the patient's intestinal flora changes over a certain period. We use each treatment element in proportion to each other and produce engineering bacteria drugs according to this ratio, and provide the patient with the best bacterial adjuvant for his situation. We will also customize a diet plan for the patient and ask him to record his daily diet to predict changes in his intestinal flora in advance. Until the next patient's stool sample is received, analysis and testing will be performed again. Thus, the entire treatment progress is carried out in this closed loop. We believe this will significantly promote the application and development of genetic engineering treatments in precision medicine.
For us, treating IBD is just the first step in our ambitions. Under the guidance of the United Nations Sustainable Development Goals, we expect to build a synthetic biology-based treatment platform for intestinal flora-related diseases based on this basis shortly, which will benefit different groups in different regions.