We have completed all competition deliverables, including Wiki, Project Promotion Video, Presentation Video, and Judging Form.

We have completed the Attribution page, where we provided a detailed description of the labor division and the contributions of each team member, as well as the assistance obtained from individuals and organizations outside of our team.

We separated into four subgroups, namely Dry lab, Wet lab, Human Practices, and Production. Each subgroup took on different responsibilities in the project, as listed on the page.

We are also grateful to have received assistance from our supervisors, instructors, and advisors for their guidance and technical support.

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Attributions

We have completed the Description page, which explains our project idea. Our motivation to undertake this project stemmed from the alarming situation of NSCLC both worldwide and specifically in Hong Kong. We started by providing a background on lung cancer, particularly NSCLC. We then delved into the existing treatments available for NSCLC patients. Notably, we highlighted the challenges faced by NSCLC patients, such as the high cost of therapy and the emergence of Osimertinib resistance. To address these issues, we introduced our innovative approach: a bispecific antibody called Polyneerab, which can bind simultaneously to EGFR and c-MET to overcome acquired drug resistance. The concept and mechanism behind this unique antibody are thoroughly explained on the Description page. We offer insights into the synthetic biological synthesis process used to create Polyneerab. Ultimately, our Description page is enriched with credible references, ensuring the accuracy and reliability of the information presented.

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Description

Our contributions to future iGEM teams and the iGEM community serve as a means to share the knowledge and skills we've gained through our iGEM experience. We created and documented new parts, added them to the Parts registry, and developed a one-step cyclization and purification intein system. We provided valuable tips and troubleshooting guidance for experiments. Moreover, we conducted fundraising efforts for lung cancer and launched a podcast to raise awareness about non-small cell lung carcinoma (NSCLC). Our participation in the HK-Macau Symposium served as a platform for knowledge exchange, inspiration, and potential collaborations, aligning with iGEM's core values.

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Contribution

We have completed the Engineering page for our Wiki, detailing our project's journey through the entire engineering cycle in pursuit of our primary objective: developing a cost-effective and highly efficient production method for a bispecific antibody to combat Osimertinib resistance in NSCLC. We have explained how we iterated the cycle several times: we illustrated how we changed our design from the linear EGFR binding peptide to the cyclic peptide (DESIGN), assembled the genetic material we needed (BUILD), tested it according to our protocol (TEST), and realized that the linear peptide is insoluble in the extraction buffer in protein expression and that it is prone to degradation and instability (LEARN). Consequently, we developed a one-step cyclization and purification intein system in a subsequent iteration of the engineering cycle. Although time constraints limited us from obtaining full results, the positive control result, the cyclizing eGFP, successfully validated the functionality of our intein system for cyclizing and purifying short peptide chains in a single step.

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Engineering

We have completed a Human Practices page that demonstrates our progress and achievements in actively engaging with the wider community.

We are deeply committed to staying informed about current advancements in scientific research on lung cancer as well as the social issues surrounding the disease. To achieve this, we conducted in-depth interviews with several medical doctors specializing in relevant fields to determine the research value and seek their advice. Simultaneously, we aim to raise public awareness and understanding of lung cancer by providing accessible information and resources. To gain insight into patients' needs, we interviewed the Hong Kong Cancer Fund, an NGO, to gather valuable perspectives on treatment options. Additionally, we organized booths and fundraising activities to capture students' attention and support cancer patients. To assess public knowledge of lung cancer and its treatment, we conducted a survey to collect relevant data. Furthermore, we created reels and podcasts on various social media platforms, highlighting our project. We have also established strong partnerships with local Hong Kong universities, such as the Chinese University of Hong Kong (CUHK) and the Hong Kong University of Science and Technology (HKUST). We later facilitated the involvement of the University of Macau in the HK-Macau Symposium hosted by CUHK. Meanwhile, we presented our project at the symposium to share our ideas and experiences.

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Human Practices

The PolYneer team presents a novel composite part system that revolutionizes EGFR-binding peptide research. Our groundbreaking approach consists of three phases, each contributing to the advancement of this field.

We ingeniously employed the intein system (Sap DnaB and Mxe GyrA) splicing mechanism. This mechanism transforms the linear EGFR-binding peptide (BBa_K4774008) into a cyclic form, optimizing its stability and functionality. Additionally, we incorporated the Chitin Binding Domain (CBD) for efficient purification of the 12-amino acid short EGFR-binding peptide (BBa_K4774010). To validate the effectiveness of our system, we included control components: the scramble EGFR-binding peptide (BBa_K4774011) was used as a negative control and eGFP (BBa_K4774009) as a positive control.

We took our innovation a step further by replacing the inteins utilized in the Npu intein system. This enables one-step cyclization of the EGFR-binding peptide (BBa_K4774013), eGFP (BBa_K4774012), and the scramble EGFR-binding peptide (BBa_K4774014), resulting in improved splicing efficiency and expanded possibilities for future applications.

Our new composite part system represents a significant advancement in EGFR-binding peptide research, offering enhanced stability, purification efficiency, and splicing capabilities. PolYneer's innovative approach opens doors to further exploration and development in this promising field.

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Parts

The main goal of our team is to apply synthetic biology to combat the major hurdles of NSCLC treatments, and to bring new hope to patients by commercializing our products. To obtain more financial funding to support further research, including clinical trials, we planned to gain entry into the Hong Kong Science & Technology Parks Corporation. The first step we took was to participate in the Health Future Challenge 2023, where we proposed our ideas and business model to investors and experts. Prior to the Challenge competition, we interviewed Arbele Limited, a Hong Kong-based biotechnology and biopharmaceutical company located at the Hong Kong Science Park. They shared their experiences in establishing a start-up in Hong Kong and provided us valuable advice and insights for our business plan.

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Entrepreneurship

As part of our Human Practices initiative, we conducted interviews that provided the opportunity to engage with different professors and specialists in the cancer field and seek their guidance on how our project can benefit the community. Their valuable insights have significantly influenced our project. Initially, we discussed with Professor Mok Shu Kam to gather updated information on recent treatment strategies, especially Osimertinib, against lung cancer and to further understand the development of new mutations and activation of multiple signaling pathways in Osimertinib refractory patients. Based on this information, we further consulted with a few medical doctors specializing in oncology to prioritize the impact of our bispecific antibody, Polyneerab, on NSCLC patients. In addition, we worked with an NGO to gain insights into the specific needs of cancer patients. A T-shirt-selling campaign in collaboration with the NGO, and promotion through class sharing, booth sessions, and extensive social media, allowed us to successfully generate funds for cancer patients, as well as raise public awareness and disseminate information about NSCLC. Furthermore, in our pursuit of shaping a better future, we participated in the Health Future Challenge Competition to seek additional advice and insights for our future development.

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Integrated Human Practices