The Problem
440,000 new mid- and low- rectal cancer cases occur every year in China.
Patients often have to have their anuses removed and have a permanent colostomy on the abdomen, both significantly affecting the patients Psychologically and Physiologically.
Shortcomings of Current Therapy
Existing therapies like chemotherapy, radiotherapy and other similar treatments have massive downsides, including:
- High recurrence rate.
- Significant side effects.
- Risk of complications such as anastomotic leakage after surgery.
Bacterial Therapy
Bacterial therapy as a new way to combat cancer is on the rise. Some outstanding qualities of bacterial therapy are:
- Bacteria is simple and easy to manipulate.
- Stable treatment over a long period of time with minimal monitoring.
- Due to the nature of some bacteria, they can target tumors directly.
The Curli Fibers
In gram negative bacteria, CsgA, an amyloid protein with five repeats, nucleate around each other to form long chains called Curli Fibers. We can modify these fibers to display different groups to achieve various functions.
Oral Delivery
To treat mid- and low- rectal cancer with bacteria, we can introduce them and other associated drugs through oral delivery by turning them into enteric capsules that selectively dissolve in desired places.
Tumor Colonization of Curmino
Curmino, our engineered EcN, can target the tumor microenvironment(TME) because it thrives in the immunosuppressive area cancer cells create. Tumor necrosis makes resources abundant in the area too, encouraging Curmino growth.
Formation of UAA Incorporated Curli
Due to the resource hungry nature of cancer cells, they will gather the unnatural amino acids(UAA) we introduced. Curmino takes advantage of this and forms Curli Fibers that contain these special components.
Prodrug Activation Through a Click-to-Release Reaction
The UAAs given to the bacteria holds a special chemical group—tetrazine. We can then introduce prodrugs caged by a corresponding group—trans-cyclooctenes(TCO). When the UAAs and prodrugs meet, a biorthogonal click-to-release reaction happens that de-cages the potent cancer-killing drugs.
Cancer Cells Eliminated
Through the previous steps, we can achieve the elimination of cancer cells in a stable, controllable manner, relieving the patient of his pain and greatly improving quality of life.
Who Are We
The iGEM PekingHSC team consists of 22 undergraduate students with varied backgrounds ranging from expertise in medicine (pharmacy, basic medicine, nurse and dentistry) to experience with project design, experiments, model, entrepreneurship.
What Is Curmino
Cur- stands for Curli Fibers we engineer. -mino stands for unnatural amino acid we use. Taken together, forms the name of our system, Curmino.
What We Want To Do
We firmly believe that Curmino will greatly contributes to the patients' quality of life and will reduce the high healthcare expenditures and workloads.
With Curmino, we strive to help more patients avoid permanent colostomy, and innovate the mid- and low- rectal cancer therapies. We hereby build towards a more healthy future.
Wet Lab
For wet lab, we have gone through several engineering cycles to fully develop the Curmino system. Specifically, we have carried out the construction of strains, characterization of the CsgA insertion site, characterization of the Click-to-Release reaction, verification of cytotoxic effects, and safety design. Ultimately, we have built a complete and mature bacterial therapeutic platform to achieve prodrug release.
Dry Lab
For the dry experiment part, we integrated various modeling and simulation methods, such as ODE, quantum chemistry, molecular dynamics, machine learning and deep learning, to conduct a comprehensive and in-depth analysis for several synthetic biology and biochemistry scenarios designed in our project. We constructed several mathematical models to describe the reaction conditions in the system, we predicted the optimal unnatural amino acid insertion sites by means of molecular dynamics, we used quantum chemical calculations to obtain the energy information of the BCR, and we even constructed a deep learning model for predicting the strength of the promoter.
Human Practices
This year, in terms of IHP, in order to provide relevant information for this year's wet and dry lab, we have successively sought out four professors and one doctor. They have provided effective feedback on the safety, feasibility, and clinical data of the wet lab projects, which has strongly promoted the progress of our wet lab. In terms of dry lab, we have actively sought cooperation and carried out extensive and positive exchanges with many schools, providing some help for dry lab. You can see the work we have done in the IHP section.
Entrepreneurship
This year, in terms of entrepreneurship, we have relied on our experimental projects and actively sought paths for the transformation of results. We participated in roadshows and various business competitions, consulted with seniors engaged in related financial industries. In this process, team members have gained a lot and have developed a preliminary business mindset and plan. We continuously revised our Business Plan (BP) in the aforementioned process, improved our business logic, and provided feedback on wet experiments. While actively seeking transformation, we made our project more responsible to stakeholders. You can see our work in the entrepreneurship section.
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Even got a game!!!
