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1.1 Interview MPS II Patients

Problem

We acknowledge that there are significant gaps in our understanding of the lived experiences of families with MPS II.We are keen to explore the patient journey from the onset of symptoms, the quest for diagnosis, to the final confirmation, and the challenges encountered along the way. We seek to understand the family's considerations in selecting treatment options and their evaluation of treatment efficacy. Additionally, we aim to shed light on the broader social challenges faced by these families and the support systems available to them.

Action

Utilizing self-media platforms of doctors and patient advocates, we reached out to several families affected by MPS II. Upon their agreement to participate, we conducted in-person interviews at their homes.

Obtain

·Diagnosis: Due to its rarity，families often travel to major city hospitals for diagnosis and treatment. This journey is not only financially draining but also delays treatment, exacerbating the condition.

·Treatment: Patients we interviewed received enzyme replacement therapy (ERT) or hematopoietic stem cell transplantation (HSCT).

·MPS II presents challenges in timely diagnosis, lengthy diagnosis and treatment periods, and exorbitant expenses, imposing severe economic and emotional burdens on families.

·Access to MPS II information is limited, but patient networks provide some support.

·Administrative hospital staff and community workers' lack of knowledge hinders processes like inter-hospital referrals and disability certification.

Feedback

Through these interviews, we gained a deeper understanding of the hardships faced by MPS II patients during diagnosis and treatment. To further our research, we plan to conduct broader surveys to analyze the broader societal impact of MPS II.Families expressed a desire for increased MPS II awareness, hoping their stories would reach other affected families for early detection and treatment. In response, we are planning an outreach campaign targeting diverse groups, including kindergartens, communities, primary schools, and universities, to raise awareness about MPS II.

1.2 China Alliance for Rare Diseases

Problem

As a result of the initial interviews, we have gained insight into the complex landscape of MPS II through the individual perspective. However, given the rarity of MPS II with an incidence rate as low as 1 in 100,000，the size of the patient population is relatively limited, requiring us to adopt a more refined data analysis strategy to enhance our understanding of this particular patient population.

Action

Through our efforts, we have established a connection with China Alliance for Rare Diseases , which is an important platform that focuses on the needs of rare disease patients and promotes the development of the rare disease industry.

Obtain

·We obtained the “Report on living condition of patients with mucopolysaccharidosis type II in China” published by a joint group of the China Alliance for Rare Diseases and Dalian Medical University.

·The report points out that patients are usually diagnosed during the critical period from 0 to 4 years old, and IDS enzyme activity test becomes an important tool for diagnosis.

·Patients have multiple organ involvement, with a high percentage of mobility and intelligence affected.

·At present, the main treatment methods for MPS II are still ERT and HSCT

·Existing treatment options are not sufficient in terms of economy and effectiveness, which brings another heavy financial and treatment burden to the patient's family.

Feedback

We need to learn more about the therapeutic status and significant shortcomings of the existing drugs in order to refine and expand the depth of the project.In addition, we found that it is imperative to raise public awareness of MPS II ,therefore, we decided to use the campus as the starting point for the campaign, and organized activities such as clay crafts and charity sales, postcard coloring and exchanging.In the future, we will do our best to make more meaningful promotional activities go beyond the campus to the general public to popularize MPS II and enhance public acceptance.

1.3 Interview--Doctor--Ying Yang

Problem

After getting the main treatment methods and data of MPS II patients, our team still has some issues with their diagnosis and treatment experience. We hope to gain a deeper insight of the difficulties faced by diagnosed and undiagnosed patients, and contribute to the patients.

Action

Our team interviewed Dr.Yang , a pediatric genetic counselor from Xi'an Children's Hospital, who specializes in laboratory techniques related to genetic testing, genetic testing data analysis, genetic counseling and interpretation of genetic testing reports.

Obtain

·Although the rapid rise and development of gene sequencing and gene therapy technologies have made it possible for more and more rare diseases patients to be diagnosed and cured, genetic counseling has not yet been popularized in major hospitals in China, and many hospitals are relatively lacking in diagnostic capabilities and related diagnostic technologies.

·For families with genetic diseases, genetic counseling is an important part of eugenics and an important step to reduce birth defects, but most families do not have a high awareness of genetic counseling.

Feedback

There is still a long way to go in the promotion of genetic counseling and rare disease related knowledge, so we have carried out scientific publicity on rare diseases, newborn screening and genetic counseling in Xi'an Children's Hospital as well as in some communities, to the public and to enhance the society's attention to the rare disease groups. In the future, we will continue to publicize the importance of genetic counseling，so that rare diseases will not be rare and every child will be healthier.

2.1 Interview--Professor -- Long Guo

Problem

We are seeking to collaborate with an expert with profound expertise and experience in the field of rare diseases to provide a clear perspective for more precise research directions. We need to determine a specific treatment therapy.

Action

We have established contact with Professor Long Guo,a distinguished scholar at the Laboratory Animal Science Department of the Basic Medical College, Medical Department of Xi'an Jiaotong University, and a visiting professor at the Medical Genetics Center of the Northwest Women and Children's Hospital. He is renowned for his substantial expertise and contributions in genetics, particularly in elucidating the pathogenesis and disease models of rare and genetic disorders.

Obtain

·Professor Guo highlighted the challenges posed by the high genetic heterogeneity, low prevalence, and diverse clinical manifestations in rare diseases.Genetic diagnosis presents a promising avenue for accurate identification of rare diseases.

·He introduced the concept of gene therapy, targeting specific genetic mutations that cause rare diseases through the introduction of normal genes or editing of aberrant ones to correct or compensate for disease-induced abnormalities.

·At the same time, he also emphasized that gene therapy is a complex field with high operational difficulty and cost. Ethical and legal issues are also the problems it faces.

Feedback

The insights gained from our conversation with Professor Guo have significantly enriched our project's accumulation. Gene therapy, with its ability to precisely address the root causes of diseases, holds immense potential for improving treatment efficiency in genetic and rare diseases. However, it also presents numerous challenges and limitations in practical application, such as high treatment costs, limited patient accessibility, ethical dilemmas, uncertainties regarding long-term effectiveness and safety.We are now acutely aware that the vastness and depth of the rare disease field far exceed our current boundaries of understanding. We should explore and consider other therapeutic approaches comprehensively and deeply to seek the best solution for our research goals.

2.2 Determine Therapy

Problem

Although we now have preliminary knowledge of treatment methods such as enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HCST), and gene therapy. However, we must acknowledge the limitations of these therapies. We need to find more optimized and innovative treatment strategies to achieve the dual goals of efficient and economically reasonable treatment

Action

Our team members brainstormed together and reviewed literature to learn about the latest advances in disease treatment. And we got in touch with a pharmaceutical company in the related field - CANbridge , a company focusing on biotech therapies for rare diseases. We obtained the latest research information and medical status of MPS II through them.

Obtain

·We have learned about two types of drug delivery systems : Liposomes and Exosomes

·Liposomes have the ability to load hydrophilic and hydrophobic drugs. However, it may undergo physical and chemical changes during storage and transportation, which can affect drug efficacy. The relatively large size may increase the difficulty of targeting to specific cells or tissues.

·Exosomes can carry a variety of proteins, lipids, RNA and other important information, can be used as a natural drug delivery vehicle. Exosomes have low immunogenicity , and their outer membrane protects the contents from degradation by external RNases. Exosomes are small enough to be directly taken up by cells improving the efficiency of action.

·MPS II patients have a higher likelihood of producing antibodies through exogenous enzyme supplementation due to their congenital deficiency of IDS.

Feedback

Among the many alternative strategies, exosomes have stood out due to their unique biological characteristics and significant therapeutic advantages. Our team finally decided to take exosomes as the core target of our project research and development: to construct engineered exosomes that carries IDS enzymes and enters the MPS II patients' tissues to reduce the storage of GAGs, so as to alleviate the patients' pain. We constructed and expressed the first generation of plasmids, however, the ability of the first generation of exosomes to carry IDS did not meet our expectations.

2.3 Construct Second-generation Plasmids

Problem

After constructing the first generation of plasmids and obtaining a stable transfected cell line, we found that although IDS was highly expressed in the cytoplasm of the stable transfected cells, the levels of IDS in the first generation of exosomes did not show significant upregulation. This indicates that the ability of the first generation of exosomes to carry IDS did not meet our expectations.This necessitates a reevaluation of the methods for enhancing the expression of the target protein in exosomes.

Action

We consulted with Professor-Feng Guan ,from Northwestern University, an expert deeply involved in the field of extracellular vesicles.

Obtain

Regarding the issues we are facing in the wet lab, Professor Guan provided us with several new ideas:

•Attach an exosomal signal peptide element (Exosignal) to the terminus of the target protein to facilitate its sorting into exosomes.

•Fuse the target protein with exosomal constituent proteins, which can promote the loading of the target protein into exosomes.

•Utilize chemical modifications, such as coupling the target protein with cholesterol, to enhance the targeting ability of exosomes toward the intended cells.

Feedback

Based on this understanding of the biological mechanism, our team designed and constructed a performance-optimized second-generation plasmid vector.The results clearly indicated that the target protein IDS not only achieved significant high expression in the cytoplasm but also demonstrated a satisfactory expression level in exosomes，with its expression abundance fully meeting our expected standards.However, when applying these research results to monolayer cell uptake experiments, we encountered a challenge: although the second-generation exosomes showed excellent performance in preparation and characterization, their uptake efficiency by cells did not meet our expectations. Therefore, our next steps will focus on optimizing plasmid design, improving exosome production process, and exploring new strategies to enhance cellular uptake.

2.4 Interview--Doctor- Yuesheng Liu

Problem

The IDS enzyme is highly expressed in the second-generation exosomes we constructed, and this abundance has reached the expected level. However, given our limited understanding of the clinical therapeutic drugs currently used for MPS II, particularly their clinical limitations, we have decided to delve deeper into the treatment status of existing drugs and their core shortcomings in clinical applications.

Action

We are honored to have had a conversation with Dr. Yuesheng Liu, a pediatric expert from the Second Affiliated Hospital of Xi'an Jiaotong University. As the attending physician and key member of the multidisciplinary treatment team for MPS II patients, Dr. Liu has provided us with valuable insights.

Obtain

•Dr. Liu pointed out that enzyme replacement therapy is used in the clinic to improve the condition of MPS II patients by intravenously delivering the enzyme aedo-glucuronide-2 sulfate esterase, which is deficient in MPS II patients into the body.

•The shortcoming of the current treatment is that the drug does not cross the blood-brain barrier , the glycosaminoglycans in the patients’ central nervous system cannot be degraded and metabolized.

Feedback

In order to more accurately identify and understand the problems caused by the blood-brain barrier during the treatment process, and to obtain more direct feedback on the treatment effect from the patient's perspective, we conducted follow-up visits to the families of patients with intellectual impairment who had received enzyme replacement therapy. Feedback from families confirms that existing therapies do have significant limitations in overcoming the blood-brain barrier.The experimental results show that although we have made some progress in optimizing the design of second-generation exosomes, the efficiency of their penetration through the blood-brain barrier and their effective uptake by cells still needs to be improved.

2.5 Construct Third-generation Plasmids

Problem

We gained awareness of the challenges facing the next-generation exosomes: a need to enhance uptake efficiency by target cells and the capacity to cross the blood-brain barrier. Tackling both issues simultaneously presented us with a daunting yet crucial challenge. Hence, there was an urgent requirement for a clear and specific research direction that would ensure accuracy and relevance in our plasmid modifications.

Action

We communicated with Professor Lei Lei, a distinguished authority in the extracellular vesicle field, particularly noted for her expertise in exploring exosomes as advanced drug delivery vehicles.

Obtain

•Professor Lei highlighted the scarcity of methods using exosomes as drug carriers for central nervous system targeting, with most research remaining experimental.

•To boost engineered exosome uptake by target cells and cross the blood-brain barrier, she recommended surface modification to facilitate more effective transmembrane transport and improved barrier penetration.

•In constructing the next-generation plasmid, she advised minimizing the inclusion of non-essential proteins, focusing instead on widely expressed cellular proteins with similar functions.

Feedback

Through extensive literature review, we integrated the coding sequence of TAT peptide (a cell penetrating peptide) into the third-generation plasmid.In our monolayer cell and in vitro blood-brain barrier models, third-generation exosomes significantly enhanced cellular uptake, thereby improving the efficiency of drug or therapeutic molecule delivery. In addition, third-generation exosomes have achieved a higher proportion of blood-brain barrier crossing than ever before.This progress marks a significant stride toward overcoming the central nervous system's delivery challenges.

3.1 Public Welfare and Promotional Activities

Purpose

There are more than 60 million rare disease patients in China. Behind this number is the resilience and hope of countless families facing unknown challenges, as well as a huge need that society must address and care for. Therefore, we are committed to building a bridge that connects all sectors of society with this special group of understanding and empathy. Through multi-dimensional and publicity campaigns, we aim to expand the boundaries of the public's awareness of rare diseases，provide patients with spiritual and economic support.

Action

•In collaboration with Sails of Hope, a rare disease charity organization in London, we conducted a charity sale on High Street in Oxford, attracting people's attention by displaying traditional Chinese artworks and postcards. And we raised public awareness of MPSII Mucopolysaccharide Storage Disorder by distributing brochures and giving presentations.

•“Glycosaminoglycan baby” is the name we give to children with MPSII, and we attracted the public to participate in the charity sale by combining the traditional Chinese non-heritage culture - sugar painting.

•We organized students to participate in clay-making activities on campus, and all the finished products were sold for charity, and all the money gained would be donated to the Rare Disease Public Welfare Organization.

Feedback

We are pleased to see that the series of public welfare activities that we have implemented have truly realized the leap from concept to action. This series of activities not only built a bridge connecting public welfare organizations and families of patients with rare diseases, but also inspired the community to pay more attention to and provide selfless assistance to this special group of people with MPSII rare diseases. All of participants have different feelings and thoughts, but all of them mentioned one thing in common: MPS II rare diseases have received more attention, and more and more people are beginning to understand and help the disadvantaged groups of rare diseases to alleviate their social pressure and financial burden. Our project will continue to play a positive role in the world.

Yuchen Shi

Manager, CANbridge Company

Yuchen Shi

Obtain:Ms. Shi emphasized that social practice should begin with a clear understanding of one's objectives and the target audience, designing activities with specific aims in mind. She suggested categorizing relevant stakeholders for our project, which explores novel therapies, into distinct groups such as patients and their families, medical professionals, university faculties, and other segments of society, with the latter potentially further classified by age or profession. By analyzing the needs of each group, our efforts could be more precisely aligned with achieving our goals.

Feedback:Following team deliberations, we decided to tailor our social practices for each demographic. For patients and their families, we conducted visits and surveys to gain insights into their living conditions and the efficacy of current therapies, providing a clear focal point for our project. When interacting with medical professionals, we sought to understand the strengths and weaknesses of existing treatments to identify areas for innovation. Engaging with university faculties, we presented our project to receive constructive feedback for improvement. For the broader public, our primary objective was to enhance public awareness of health and synthetic biology. To this end, we organized engaging classes for kindergarteners, lectures in universities, and conducted surveys and awareness campaigns in communities.

3.2 Community Research and Promotion

Purpose

Patients with rare diseases often face physical deformities or obstacles in intellectual development. These challenges not only profoundly affect their daily lives but also may lead to misunderstandings, prejudices, and discrimination in society.We aspire to enter communities and through scientific explanations, vivid case sharing, and sincere interactive exchanges, promote the elimination of public prejudices and misunderstandings towards patients with rare diseases on the one hand, On the other hand, we hope to spread synthetic biology, a cutting-edge technology, to demonstrate its boundless potential and hope in treating rare diseases, conquering complex diseases, and advancing personalized medicine.

Action

We conducted a questionnaire survey to gain an understanding of the level of awareness towards rare diseases and synthetic biology among people of different age groups. We distributed science popularization brochures, promoting rare diseases and popularizing synthetic biology through various forms . We actively disseminated these brochures to residents, hoping that they could take them home and learn together with their families, thereby further broadening knowledge and learning of synthetic biology.

Feedback

The science popularization brochures we prepared significantly enhanced residents' acceptance of scientific knowledge. Residents are filled with anticipation and visions for the vast application prospects of synthetic biology in fields such as healthcare, environmental protection, and agriculture. Particularly noteworthy is the unprecedented surge in residents' attention and concern for rare diseases during this event. They began to realize that frontier technologies like synthetic biology hold the key to bringing hope and light to these special groups. Many residents expressed their intention to actively disseminate the knowledge they had learned, contributing their part to building a more inclusive and supportive social environment.

3.3 Exchange with Pharmaceutical Company

Purpose

NWU-CHINA-A conducted an interview with the regional manager of CANbridge company regarding the clinical progress and market performance of MPS II. CANbridge company is a significant player in the biopharmaceutical field, focusing on the development and commercialization of innovative therapies for rare diseases and rare tumors. We also seek to learn about the latest data on currently applied clinical treatment methods, including efficacy assessments, safety considerations, and patient feedback.

Obtain

•Enzyme replacement therapy is currently undergoing cross-sectional clinical trials. By deeply analyzing the impact of genotype and phenotype differences on therapeutic efficacy, there is hope to further improve the effectiveness and specificity of the treatment.

•The key factor in the public and patients' acceptance of treatment methods is not whether they are new, but whether there are clinical trial data to prove their effectiveness and convenience.

•The current core challenge faced by rare disease treatments is the contradiction between high costs and the small number of patients. The high prices of medications stem from significant research and development costs alongside a limited patient base, which restricts market expansion.

Feedback

The exchange between NWU-CHINA-A and CANbridge company revealed the latest clinical advancements in the treatment of MPS II, provided a profound analysis of the current market situation and challenges, offered valuable insights for future treatment strategies and market positioning. We have tentatively invited the person in charge to participate in an online public awareness event aimed at enhancing public awareness of rare diseases, reducing misunderstandings and prejudices, and laying a social foundation for the promotion of innovative therapies.

3.4 Science Communication Conference and Education Lecture

To further enhance public awareness of synthetic biology and collaborate with various sectors to elevate attention and education on rare disease issues, we have meticulously planned and implemented a series of science popularization activities across different age groups. we aim to sow the seeds of science in every corner, igniting interest of life sciences, especially among the younger generation. According to statistics, this series of science education activities has attracted over 200 students from different age groups, yielding significant results. For more details, please click the SDG education section.

4.1 Communication with UM-Macau

Purpose

In order to ensure the smooth progress and successful completion of the project, effective communication with other teams has become an indispensable link. It is not only a key link for information flow, but also a solid foundation for building teamwork, efficient problem-solving, and continuous progress. In every stage of the project's progress, fresh information, valuable experience, skilled techniques, and cutting-edge knowledge will be freely circulated and broadened through active communication and interaction, promoting the enrichment and expansion of the overall knowledge base.After attending the CCiC Synthetix Biology Conference, we were delighted to find that the UM-Macau team was also focusing on exosome therapy this year. The students from both wet lab teams engaged in in-depth exchanges and sharing of project-related details.

Action

The team leaders of the wet lab of both parties had an in-depth discussion on the cell lines that generate exosomes, the resistance genes used to screen for stable transfection, and other key plasmid elements. Students from UM-Macau detailed the resistance genes they use to screen stably transfected cells, as well as the problems they are currently facing in the wet lab. Students from NWU-CHINA-A introduced the plasmid element that promotes the level of target protein in exosomes, explained its molecular mechanism, and finally recommended relevant references.

Feedback

The wet lab of the two sides is highly similar in terms of experimental materials and project development methods, and because our team has accumulated more experience in the wet lab, we have provided some practical suggestions to the wet lab of UM-Macau in this exchange. The communication with the UM-Macau team has also broadened our horizons and provided us with new ideas and continuous motivation for the development of the wet lab. Through this high-quality exchange and interaction, the relationship between the teams of the two universities has become closer, which has laid a solid foundation for long-term cooperation in the future. We firmly believe that with the joint efforts of both parties, we will be able to achieve more outstanding results, work together to promote the development of synthetic biology, and contribute to the benefit of mankind and the construction of a better future. This exchange has is very beneficial, and we sincerely look forward to the continuous deepening of the cooperation between the teams of the two universities to promote the in-depth development of synthetic biology research.

4.2 Communication with SZPU-CHINA

Purpose

Given the safety, ethical, and ethical considerations inherent in the field of synthetic biology, our team is highly vigilant and responsible at every step of the project, with a particular focus on these dimensions of due consideration. We are committed to actively communicating and cooperating across teams, drawing on the wisdom and experience of many parties, in order to effectively avoid potential risks and jointly make a responsible and sustainable path for scientific progress.

Action

The team of SZPU-CHINA , an iGEM team from Shenzhen Polytechnic University, participated in the project on the control of Carbapenem resistant Acinetobacter baumannii (CRAB). NWU-CHINA-A and SZPU-CHINA held their first online meeting. The purpose of this conference is to enhance the understanding of each other's projects, share the experience of the two teams in the field of synthetic biology in the field of safety, and ethics, and explore the possibility of future cooperation to jointly expand the impact of both projects while anticipating and preventing potential risks.

Feedback

We realize that the purpose of scientific research is to improve human well-being. By focusing on safety, ethics and morality, scientific research can be steered in a healthier and more sustainable direction. This helps to prevent scientific research from deviating from its original purpose and ensures that scientific and technological achievements can truly benefit mankind.With the rapid development of synthetic biology, mankind is facing more and more unknown challenges. By considering and evaluating the safety, ethical, and moral implications of synthetic biology in advance, we can prepare for these challenges and formulate scientifically sound policies and measures to ensure the long-term stable development of human society.

5.1 China Rare Disease Conference

The China Rare Disease Conference has become a significant force driving the advancement of rare disease prevention and China's rare disease treatment in the country since its inception in 2019. It aims to interpret the latest policies in China's rare disease industry and propel the development of safeguard measures for rare disease prevention and treatment. Our team is prepared to participate in this event in Beijing from October 18th to 23rd, 2024. We will present in detail the latest progress of our project, eagerly anticipating profound exchanges and discussions with experts and peers from government agencies, academia, the medical community, the pharmaceutical industry, and patient organizations.These insights will aid us in ensuring that our efforts precisely address the actual needs of MPS II patients, bringing them substantial assistance and improvement.

We will actively engage with government departments, policymakers, and industry experts to stay informed of the latest policy trends and orientations, exploring ways to provide more support and safeguards for MPS II patients at the policy level. Simultaneously, drawing upon the practical experiences of our iGEM Integrated Human Practice, we will propose targeted policy recommendations and institutional frameworks, contributing our wisdom and strength to the institutionalization and standardization of MPS II prevention and treatment efforts.

We believe that through collaborative efforts, resource sharing, and complementary advantages, we can jointly tackle the challenges and difficulties in rare disease prevention and treatment, creating a brighter future for patients with MPS II and other rare diseases.

Jing Tian

PhD, professor of the School of Life Sciences, Northwest University, doctoral supervisor

Jing Tian

Obtain:In constructing a comprehensive scientific inquiry project, ethical considerations are indispensable. After information inquiry and team discussion, we approached Professor Jing Tian and sought her advice. She pointed out that patient feedback and follow-up visits are of great importance, which not only allows patients' voices to be heard and respected, but also provides invaluable references for the optimization of research. Follow-up visits, moreover, express continuous care for patients, especially those with rare diseases, by offering them necessary medical advice and psychological support.

Feedback:Following Professor Tian's advice, we conducted follow-up visits to the patient families we had interviewed previously. During these visits, we introduced the technology of exosome therapy, and inquired about their suggestions on the current technologies, as well as their perspectives and acceptance levels towards exosome therapy. Concurrently, we established a partnership with the "Sails of Hope" organization, which has long been dedicated to medical assistance, psychological support, and public education for patients with rare diseases. Together, we aim to unite more forces and jointly create a sky of hope for this special group of individuals.

Xinbao Xie

Medical Doctor, Associate Chief Physician, Children's Hospital of Fudan University.

Xinbao Xie

Obtain:Dr. Xie possesses profound medical expertise and years of accumulated clinical experience in pediatric treatment. As MPS II is most commonly found in children, he emphasizes the significant differences between children and adults in terms of physiology, psychology, and disease manifestations. When formulating future treatment plans, it is necessary to fully consider the impact of children's growth and development stages on drug response, metabolic rate, and tolerance. Additionally, attention should be paid to the psychological state of patients, and necessary psychological support and intervention should be provided.

Feedback:We fully agree with Dr. Xie's viewpoint, which reflects the doctor's profound understanding and humanistic care for pediatric patients ，also provides important guidance for the future research direction and strategy of our project. We have a clearer understanding that while pursuing advancements in medical technology, we must always prioritize the feelings and needs of patients. We have also shared this suggestion with relevant doctors and researchers we have previously collaborated with, hoping that through such exchanges, we can inspire more thoughts and discussions on how to better serve patients and jointly promote the progress and development of the medical industry.

5.2 Patient Feedback and Technical Outlook

We aim to understand patients' acceptance of engineered exosome therapy, which will help identify potential market demand. By gathering patient feedback, we can focus on key ethical considerations, ensuring that future human trials fully respect and protect patient rights. Additionally, we need to know about patient families' satisfaction with this new treatment and their unmet needs, clearing the specific problems that engineered exosome therapy can address.

To achieve this, our team conducted follow-up visits with patient families to introduce this therapy technology as well as their views on and acceptance of it. Patients and family members expressed strong support for this therapy, believing it to be more effective than other treatments for MPS II and hopeful that it will significantly improve patients' quality of life. Through their feedback, we also gained insights into potential ethical, psychological, or social issues they may face. We will consider these factors in our future outreach efforts to mitigate potential challenges and better meet patients' actual needs, while also setting realistic goals and expectations for the research team.

Patient families are filled with immense hope, eager for this therapy to be applied in practice as soon as possible. They long for this to allow more patients to break free from the shackles of pain and move toward a future filled with sunshine and hope.

5.3 Ethics and Morality

Project process：In the ethical and safe practice of rare disease research, we are aware of the social prejudices and discrimination faced by patients due to the uniqueness of their illnesses. Therefore, throughout the entire research process, we rigorously anonymized the identity information of three MPS II patient families, firmly protecting the privacy of patients.We resolutely safeguard the autonomy, right to know, and privacy of the interviewees. All interviews were conducted voluntarily by the interviewees, and interview questions were answered voluntarily. All written records, photographs, audio recordings, and videos were released only with the consent of the interviewees.

Future plans：We are focused on the research itself, and also committed to providing continuous care for patients and maintaining close contact with their families after the project is completed. We will promptly respond to their needs and provide timely support and assistance. In the future, we will continue to monitor their living conditions, promptly address their difficulties and needs, and offer support and assistance within our capabilities. We are dedicated to translating our research findings into practical applications, presenting them at upcoming rare disease conferences, and promoting the availability and medical insurance coverage of future therapeutic drugs, thereby alleviating the burden on patient families. We strive to demonstrate the humanistic care and social value of scientific research through concrete actions.

Technical considerations：The future implementation of engineered exosome therapy for MPS II necessitates comprehensive efforts and considerations across multiple dimensions, including technology, ethics, and communication, with a patient-centric approach that respects life and pursues excellence. It is crucial to ensure that patients and their families fully understand the experimental nature of the treatment, potential risks, expected benefits, and alternative treatment options.Establishing a long-term follow-up and feedback mechanism to continuously monitor patients' treatment progress and changes in quality of life, and promptly adjusting treatment strategies, is key to ensuring the sustained effectiveness and safety of engineered exosome therapy. At the same time, this also provides valuable clinical data and experience for future research, driving continuous technological advancements and development in this field.