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Drawing Scientific Inspiration from Personal Experience

When defining our iGEM project, our selection was not only a product of brainstorming but also rooted in the genuine experiences of our team members. We connected online with a patient suffering from MPS II, and through a brief conversation, we gained deeper insights into the impact of this disease on patients, which sparked our initial understanding. Furthermore, we recognized the significant challenges in the treatment landscape for rare diseases like MPS II, prompting us to consider how synthetic biology could be applied to address this condition. This approach not only aligns with the mission of the iGEM competition but also holds substantial practical significance.

We understand that confirming a project idea is often a lengthy and challenging process. Therefore, we encourage future teams to reflect on their project choices through personal experiences and to remain attentive to inspirations from everyday life, as this is crucial for the sustainable and innovative development of both iGEM and synthetic biology.

Innovations regarding MPS II-related therapies

Currently, enzyme replacement therapy is the primary treatment for MPS II; however, it has significant limitations: patients require weekly infusions, the treatment is costly, and it cannot penetrate the blood-brain barrier, failing to alleviate central nervous system damage. This project involves the iterative development of three plasmids, ultimately integrating the IDS gene into the cell genome. Additionally, we modified the exosomal membrane by fusing the cell-penetrating peptide TAT with the LAMP2A gene to enhance the exosome's ability to traverse the blood-brain barrier, thereby reducing the accumulation of glycosaminoglycans in the patient's brain and overcoming the limitations of existing therapies.

Our proposed novel treatment strategy integrates innovative methods from synthetic biology, aiming to effectively improve the targeting and efficiency of treatment. Furthermore, this approach not only has the potential to enhance the quality of life for patients but also offers insights for the treatment of other central nervous system disorders. It provides new directions and ideas for future MPS II research, facilitating substantial breakthroughs in therapeutic efficacy.

New parts on the registry

During this year's project implementation, our team proposed several feasible composite parts that not only demonstrate innovation in design but also show promising functionality and application potential. These composite parts have undergone rigorous experimental validation, aiming to enhance the efficiency and effectiveness of synthetic biology applications. We hope that by sharing these research results and practical experiences, we can provide valuable advice and references for future iGEM teams, assisting them in advancing their projects smoothly, avoiding previous mistakes, and contributing to the overall progress and development of the field of synthetic biology.

After the BBa_K5499013 sequence is integrated into the lentiviral expression vector, the transfected HEK293T cells will express large amounts of IDS. Even if IDS cannot be extensively sorted into exosomes for use in our project, future iGEM teams interested in the cellular synthesis of IDS can use it as a reference;

After the BBa_K5499010 is integrated into the lentiviral expression vector, the transfected HEK293T cells will secrete exosomes containing large amounts of IDS. Future iGEM teams interested in using exosomes as drug delivery carriers can refer to this composite part;

After the BBa_K5499011 is integrated into the lentiviral expression vector, the exosomes secreted by the transfected HEK293T cells will exhibit significant properties, such as crossing the blood-brain barrier and other biological barriers. Future iGEM teams aiming to treat central nervous system diseases can consider this composite part as a drug delivery carrier;

BBa_K5499012 is the final product of our team’s project iteration. BBa_K5499012 combines the expression characteristics of both BBa_K5499011 and BBa_K5499010. Its multi-cistronic feature on a single expression vector greatly reduces the burden on the chassis organism, avoiding competition between multiple expression vectors, making it highly promising for industrial and commercial applications.

Studies on exosomes as drug-carrying delivery systems

Exosomes are extracellular vesicles secreted by cells, with diameters ranging from 30 to 100 nm. Scientific research has demonstrated that engineered exosomes, after modification, possess significant potential as drug carriers for the treatment of brain diseases. In this experiment, we constructed engineered exosomes to carry the IDS enzyme across the blood-brain barrier, thereby alleviating central nervous system damage in MPS II patients.

The implementation of our project will provide additional therapeutic strategies and application possibilities for engineered exosomes as drug delivery systems, integrating them with synthetic biology to inspire future teams to conduct more in-depth research. Through our technical innovations, future teams can explore various exosome modification and functionalization strategies to enhance drug targeting and release efficiency in target tissues. Additionally, by utilizing tools from synthetic biology, these teams can design more complex drug delivery systems that achieve multifunctionality, ultimately providing more effective treatment options for patients.

Laboratory Skills Manual

Molecular biology experiments are a core component of synthetic biology projects. However, for beginners, relying on kit instructions can often lead to operational errors and make it challenging to gain a deep understanding of the principles and significance of each step. Therefore, based on our experiences during the iGEM project, we have compiled the "Northwest University Molecular Biology Laboratory Skills Manual," which systematically covers common molecular experimental techniques.

We hope this manual can provide effective guidance for future teams in their experimental endeavors.

References for future teams on human practices

After defining the project and its core values, we undertook a series of human practices activities. Throughout this process, we focused on stakeholders; in addition to conducting expert interviews and communicating with relevant organizations, we maintained close contact with patients. After acquiring academic knowledge related to treatment, we promptly followed up with the patients' families and used their feedback to further refine our project.

Moreover, we established long-term, effective communication with patients, providing them with care and support not only during the project advancement but also in their daily lives. This approach ensured that our project focused not only on academic progress but also placed a greater emphasis on the dimension of humanistic care.

Therefore, we recommend that future iGEM teams actively engage with stakeholders during both human practices and project advancement, as this is crucial for the successful implementation of their projects.