Wet Lab

We appreciate the iGEM competition's commitment to open-source collaboration and the practice of building upon the experiences of past iGEM teams. During our project brainstorming and research phase, we extensively reviewed the efforts and findings of previous iGEM teams. Their work served as a valuable source of inspiration and guidance for us throughout the season. That's why we were dedicated to ensuring that our team made a meaningful contribution to the iGEM competition, with the intention of providing a foundation for future teams to further develop and expand upon our work.

Parts

Firstly, we contributed to the iGEM community by documenting our antigen selection and plasmid design strategies which you can see at our Experiments page. Secondly, we contributed to the part library, by adding information from literature to fifteen basic parts. Next, we added one composite part in the iGEM registry with the essential, in-depth details. The parts from BBa_K5017000 to BBa_K5017007 are designed by the Wet Lab and include information about the Chimeric Antigen Receptor (CAR) and its components. At the same time, the parts from BBa_K5017008 to BBa_K5017015 are developed by the Dry Lab subteam with the software DiffAb, using a binding optimization algorithm for the antigen MSLN-scFv (Part BBa_K5017002).

Literature information about an innovative and currently unknown drug delivery method

According to bibliographic research conducted by our team, we concluded that, so far, the most effective therapeutic approach for pancreatic cancer is surgical resection, which occurs only when there are no metastases, an exceedingly rare occurrence in pancreatic cancer. One of the risks of surgery in the pancreatic region is postoperative bleeding. Furthermore, recurrences after surgical resection of PDAC are unfortunately common, the rate being as high as 80%, even after R0 surgery where no cancer cells seen microscopically at the primary tumor site.

What if we prevent postoperative bleeding while simultaneously reducing the chances of recurrence?

Our potential breakthrough therapy delivery system to address this problem is based on a recent study published in Science Advances developed by researchers from the University of Pennsylvania and offers hope for addressing solid tumor recurrence. The researchers introduced CAR-T cells into a specially designed fibrin gel used for preventing post-surgery bleeding. Applying this gel to the surgical wounds of 20 mice immediately after resecting hard-to-treat tumors led to the prevention of recurrence in 19 of them, all without hindering the healing process. The promising results have prompted plans for human trials.[4] Based on this work we propose the introduction of CAR-NK cells targeting mesothelin for the treatment of PDAC into an existing product called Tisseel, a fibrin sealant manufactured by Baxter, which surgeons commonly use to control bleeding in challenging surgical sites. It consists of two components: a fibrinogen solution and a thrombin solution. When these two components are mixed, they initiate a process which mimics the body's natural blood clotting mechanism. By carefully adjusting the concentrations of the gel's components we can ensure that CAR-NK cells would not migrate too far from the target area while still reaching the tissue surrounding the tumor.

This drug delivery method is one of the three we will propose as part of the competition, and you can learn more about it on the implementation page

By proposing this groundbreaking drug administration to the patient, we aim to shed light on the significance of reducing immediate post-operative complications and decreasing the likelihood of disease recurrence in the future. Furthermore, in this way, we aspire to set an inspirational example for future iGEM generations to discover and propose effective drug delivery methods that alleviate the patient's concern about potential future relapse.

A novel Molecular Dynamics Simulation

Furthermore, the Dry Lab subteam during the Molecular Dynamics Simulations activities and in order to closely replicate the in vivo behavior of our Chimeric Antigen Receptor (CAR), aimed to create a model of the cell membrane surrounding it, which is a novel part in Molecular Dynamics Simulations in the context of the iGEM Competition. More information about the model of the Chimeric Antigen Receptor and the cell membrane surrounding it you can find here

Entrepreneurship

Guide to entrepreneurial development

In this guide we gather valuable lessons we learnt in our journey of working towards the entrepreneurial development of our idea, which may serve as insightful advice for future iGEM teams, in order to efficiently advance their business and end product. You may also download our guide here.

1. 1. How to make your product stand out:
   • Identify customer needs and try to meet them
   • Identify possible market gaps your product could fill
   • Set well-determined goals for the place your product is going to take in the market
   • During development, take into consideration the competition arising from similar products already existing in the market
   • Plan your marketing strategy by focusing on what makes your product more innovative/efficient compared to others in the market

1. 2. How to achieve long-term establishment of your product in the market:
   • Nurture relationships with potential clients and partners
   • Build trust bonds among your end customers
   • Always strive to receive feedback from your clients
   • Readjust your product according to constructive criticism and clients’ needs
   • Create a welcoming, supporting, and inclusive working environment
   • Embrace diversity in the work environment
   • Set a realistic timeline goal for the entrepreneurial development of your idea

1. 3. Engage in conversations with finance and entrepreneurship experts:
• Network by attending conferences and events
• Directly communicate with professionals via email or calls and don’t be afraid to ask questions
• Participate in entrepreneurship and innovation competitions as an opportunity to receive mentorship from economic analysts and marketing experts

1. 4. Define the regulatory guidelines your product has to comply with:
• Communicate with National Regulatory Authorities (such as the Hellenic Medicines Agency in Greece)
• Communicate with Regulatory Authorities on an international level (such as the European Medicines Agency or the Food and Drug Administration)
• Seek consulting programs from Regulatory Authorities in order to collaborate with them to achieve more efficient product development
• Ask questions to Regulatory Affairs professionals from the Industry or Regulatory Authorities

1. 5. Align with sustainability goals and Corporate Social Responsibility Initiatives:
• Take the necessary steps towards designing a more sustainable product/company
• Eliminate packaging materials and production waste
• Collaborate with recycling organizations

1. 6. See the bigger picture:
• Be flexible and open to following new ways of approaching your business venture
• Be creative and don’t be afraid to dive deeper into your ideas and figure out innovative solutions
• Be optimistic and don’t allow obstacles to set you back
• Be decisive and solution-oriented

1. 7. Risk management:
• Find a solution for every possible risk that could come up regarding the launch and development of your product
• Figure out how to eliminate the weaknesses of your product
• Conduct the necessary competitors' research well in advance and try to predict possible market changes in order to readapt to them

Questionnaire Template for Primary Market Research

Since Primary Market Research is a necessary step towards the entrepreneurial development of any idea, we have put together several questions we consider important to gather experts’ opinion of the product into the questionnaire template you may find below. In this way, we hope to help future iGEM teams navigate their way to market research more easily.

Graphic Design

Graphic Design Archive

On the journey of promoting and developing a project, the way that some elements, processes, lab steps, diagrams and images are represented is of paramount importance. Therefore, we decided to provide future iGEM teams, which may be working on medical projects involving CARs, Cells, Digestive Organs, and similar laboratory procedures to ours, with a graphic design archive. Specifically, we created a PDF file with our graphics that anyone can freely download and open with Adobe Illustrator or similar software tools. Feel free to alter and transform them into their best possible version to fit the needs of your own project! You will find the PDF file bellow:

Graphic Design Archive