Colorectal cancer is a common malignant tumor in the world, ranking third in the incidence of malignant tumors and second in mortality. It is also the highest incidence and mortality rate among malignant tumors of the digestive system. In recent years, the incidence of colorectal cancer has continued to increase in China, ranking second in the incidence of malignant tumors of the digestive system. In order to meet this challenge, the ROBINER project from Guangzhou, China, came into being, focusing on research in the field of colorectal cancer.The ROBINER project is committed to developing innovative colorectal cancer treatments, aiming to achieve precise targeted treatment through the application of engineered probiotics and provide patients with safer and more effective treatment options. The project team engineered the chassis microorganism Nissle 1917 so that it could attach to colorectal cancer cells. CD enzyme is used to convert the drug five-fluorocytosine (5-FC) into the chemotherapy drug five-fluorouracil (5-FU) at the lesion site, thereby achieving precise treatment of cancer cells.ROBINER's vision is to provide colorectal cancer patients with more precise, low-side-effect treatment options and reduce patients' pain and distress during the treatment process. Our team firmly believes that the drugs we develop will play an important role in the fight against colorectal cancer and contribute to improving the quality of life of patients.Here is our business plan

We choose an E. coli that is safe for humans - Nissle1917, and then we will modify the E. coliOur first part is the targeting part. We use cell surface display technology to anchor the HIpA protein on the surface of the strain through the ice nucleation protein INP. The HIpA protein binds to HSPG (heparin sulfate proteoglycan) on the surface of tumor cells, allowing the engineered strain to target and anchor to cancer cells. surfaceThe second part is the treatment part. When the strain is anchored on the surface of cancer cells, the strain expresses cytosine deaminase to convert 5-FC into 5-FU, thereby producing a local high-concentration chemotherapy effect without affecting other parts of the body.We conjugated our cytosine deaminase to ice crystal nucleoprotein and displayed it in the gut via cell surface display technology to improve bacterial survivability.See our project description for more detailshttps://2023.igem.wiki/gec-guangzhou/description

During the initial design phase, we originally planned to turn the final product into bacterial powder for drug administration. However, we found that the bacterial powder is easily corroded by gastric acid, the viable bacteria are unevenly distributed, and once the package is opened and exposed to oxygen, the preservation of the bacterial powder faces difficulties. Therefore, we decided to improve the product into capsule form for administration.As the project progressed, we found through surveys that patients with intermediate and advanced colorectal cancer are restricted in many aspects of daily life due to the invasion of the disease, especially in diet. Considering these practical issues, we finally decided to transform the product into a suppository form. Such a transformation aims to alleviate patients' inconvenience, while ensuring that drugs can reach the diseased site more accurately and effectively, providing patients with more humane and considerate treatment options.Schematic diagram

Instructions for use

We aspire to be a leader in leveraging the power of synthetic biology and genetic engineering to optimize existing treatments and explore innovative disease treatments. We hope to transform public perception of GMO, biosynthetic and genetic engineering technologies while working to build an affordable healthcare platform. Through this platform, we hope to provide solutions to people in need of medical advice, attention and products, with the goal of improving and extending people's quality of life.