INTEGRATED HUMAN PRACTICES

To ensure that our project addresses real-world needs and is socially responsible, we took a systematic and iterative approach to Human Practices. Our goal was to deeply explore how our work intersects with the broader world so that our design choices could be informed by meaningful dialogue and evidence.

We implemented a multi-pronged strategy combining online questionnaires, desk research, and in-person field surveys to understand public attitudes, identify community needs, and evaluate the social context of our solution. Surveys were strategically conducted in high-traffic areas, allowing us to capture diverse public perspectives across demographics and lifestyles.

At the same time, we engaged with key stakeholders and experts through structured interviews, including conversations with clinicians, pharmaceutical companies, and patients. These discussions provided us with important insights into current challenges in healthcare and clinical practice. In addition, we established a partnership with an igem team at Peking University, which provided deep clinical expertise and ongoing feedback.

By integrating quantitative data, expert consultation, and real-world observations, we practiced methodological triangulation to enhance the credibility of our conclusions. This comprehensive Human Practices workflow guided our project design, ensuring that it is not only scientifically robust but also ethically grounded and aligned with the needs of the communities we aim to serve.

2.1 Questionnaire on Public Awareness of Helicobacter pylori

To better understand public awareness, misconceptions, and concerns surrounding Helicobacter pylori (Hp) infections and current treatment methods, we designed and distributed a structured questionnaire as part of our Human Practices work.

Our goal was to explore the level of knowledge and the perceptions that different demographics hold about H. pylori—including its transmission, symptoms, related diseases, treatment options, and public attitudes toward antibiotic use and resistance. Additionally, we aimed to assess the general public's familiarity with novel treatment strategies, such as nanobody-based therapies, to evaluate the potential acceptability of our proposed solution.

The questionnaire collected responses from a broad demographic, including people from various age groups, occupations, and geographic regions. It included both multiple-choice and scaled questions to allow for quantitative analysis.

In this survey, we collected a total of 396 valid questionnaires, and the vast majority of respondents were female, mainly in the age group of 18-60 years old, covering a wide range. In terms of occupation, although the majority are students, it also involves multiple industries. According to statistical results, about 30% of respondents or their family members have been infected with Helicobacter pylori. This finding is not only consistent with existing research data, but also reflects that the infection rate of Helicobacter pylori in urban Chinese population is relatively high, suggesting that the public should strengthen their awareness of Helicobacter pylori prevention and scientific prevention and control capabilities.

In terms of infection detection, about 73% of those who have been infected said that they found Helicobacter pylori infection through regular physical examinations. This shows that public health awareness is gradually increasing, and regular physical examinations as an effective means of early detection should be further advocated and popularized to prevent disease delays and reduce the risk of related diseases.

In terms of the cognition of transmission methods, about 80% of respondents believe that "oral transmission" is the main transmission route of Helicobacter pylori. This reflects that the public has certain limitations in the transmission route, and a considerable proportion of the population still does not know other routes such as mother-to-child transmission, pet transmission and medical transmission (see Figure 4). Therefore, it is necessary to strengthen the comprehensive publicity of the transmission mechanism and improve the public's awareness of prevention and daily protection level.

In terms of disease symptom recognition, about 86% of the respondents believe that Helicobacter pylori may cause gastric inflammation, and 81% of the respondents believe that Helicobacter pylori may induce intestinal diseases. This shows that most people have realized the harm of the pathogen to the digestive system, but still lack a systematic understanding of the various diseases it may cause (such as gastric cancer, gastric ulcer, etc.), and it is necessary to further strengthen the popularization of relevant health knowledge.

For the competent judgment of the infection rate, only 30% of the respondents believe that the infection rate of Helicobacter pylori is 20%-40%, which means that more than 50% of the respondents still lack understanding of the actual infection situation of Helicobacter pylori. Improving the public's accurate understanding of the current infection rate can further increase the public's attention to prevention tasks.

Regarding treatment methods, 92% of respondents support the use of antibiotics for combined treatment, and a few respondents believe that surgical treatment is also an effective means of treating Helicobacter pylori. In fact, surgical treatment has not yet become a mainstream or standard treatment method, and only exists as an auxiliary solution. Therefore, it is necessary to further enhance the public's scientific understanding of mainstream treatment methods.

In addition, about 70% of respondents expressed concerns about the possible side effects and drug resistance of antibiotic treatment, which shows that the public still has great doubts about traditional treatment options, and strengthening treatment compliance and medication education is crucial. At the same time, the vast majority of respondents are still unfamiliar with "nanobody treatment", indicating that the public's awareness of this new treatment method is extremely low. In the future, we can combine the dissemination trend of emerging biotechnology to increase the publicity and education of nanobody treatment for the treatment of Helicobacter pylori.

2.2 Questionnaire Regarding Product Commercialization

This business questionnaire focuses on product form, price and market acceptance. The purpose is to understand consumers' true views on the product, so as to optimize product design, formulate reasonable pricing strategies, and evaluate market potential. Through the questionnaire, we can obtain key data such as users' sensitivity to product functions, appearance, price, and willingness to buy, and avoid the risks brought by subjective decisions.

The core goal of designing this questionnaire is to verify whether the product meets market demand and find the best path for commercialization. For example, through price testing, we can determine the price range acceptable to consumers; through product preference surveys, we can find out which functions are more popular; and the evaluation of market acceptance can help determine whether the product has enough potential users. These data can provide strong support for subsequent product improvements, marketing strategies and sales plans.

In the end, we can not only get quantitative data (such as price acceptance and function preference ranking) from the questionnaire, but also explore the deep needs of users. For example, open questions may reveal unmet pain points, and the differences in feedback from different groups of people can help accurately locate the target market. These insights can guide companies to optimize products, adjust pricing, and formulate promotion strategies, thereby improving the market competitiveness and commercial success rate of products.

Our second survey yielded 185 valid responses, the vast majority of which were female. This survey primarily targeted the 18-60 age group, encompassing a wide range of demographics. While most respondents were students, there was also participation from practitioners in various fields, such as medicine and pharmacy, making the sample representative. Statistics show that 67% of respondents have used probiotic products, demonstrating a certain level of public awareness of probiotics, which will positively impact our future R&D and marketing efforts.

Survey data shows that only 30% of respondents have heard of the term "probiotic nanobodies," and even fewer can accurately explain how they work. This reflects the limited public awareness of this emerging therapeutic approach. Further analysis indicates that awareness is strongly associated with age, education level, and geographic location. Younger people, highly educated individuals, and residents of first-tier cities show relatively higher awareness, but overall familiarity remains low. These findings underscore the urgency of raising public awareness through diverse channels and formats, such as videos, infographics, and offline engagement events.

The data further shows that up to 80% of respondents would be willing to try nanobody therapeutics if they were officially launched. This demonstrates strong public acceptance of novel biotherapeutic technologies and highlights their market potential. For us, this high level of acceptance not only lowers the educational cost of product promotion but also reinforces public trust and expectations for innovative medical solutions.

In terms of price acceptance, 48% of respondents consider 100–200 RMB to be the most reasonable price range for nanobody therapeutics. This provides key insights for our product development and commercialization strategy. Moving forward, we will target this range by balancing R&D investments with production costs, enhancing price competitiveness while ensuring efficacy and safety.

As for product form, more than 50% of respondents prefer oral capsules as the delivery method for nanobodies. This preference stems from their convenience, ease of storage and transport, and overall user-friendliness. It offers clear market guidance for determining the final dosage form. Accordingly, we are prioritizing the development of oral capsules to better align with user needs and maximize product usability.

In conclusion, public awareness of probiotic nanobodies remains limited. Moving forward, we will intensify outreach through multiple channels—such as short videos, hospital-based promotions, and expert-led talks—highlighting the safety and clinical potential of this technology. These efforts aim to boost public understanding and trust, ultimately promoting broader patient adoption.

3.1 Identification

Period: Research and Development

Other R&D teams (technical communication, technical feasibility)

Biological and ethical experts (technical feasibility)

Pharmaceutical companies (commercial feasibility)

Regulatory agencies (market access feasibility)

Period: Early stage of commercialization:

Medical institutions and hospitals (clinical application)

Patients (payment and feedback)

Regulatory agencies (market regulation)

Period: Outsourcing to overseas markets:

International regulatory agencies (market entry requirements)

Overseas pharmaceutical companies (commercial cooperation and competition)

International health organizations (corporate social responsibility)

Detailed explanation of how these stakeholders influence us:

Other R&D teams (Provide technical exchanges, analyze technical feasibility)

Our team should enhance communication with other R&D teams during the project development stage. In the early stage of product development, we can verify technical feasibility and share laboratory resources through communication. In the middle stage of product development, we need to pay attention to communication with teams from other academic fields to obtain interdisciplinary support. For example, in aspects related to product commercialization design, we can communicate with teams in marketing. In the later stage of product development, technical exchanges and comparisons with other teams help us achieve technical standardization.

Biological and ethical experts (technical feasibility and ethical norms)

Engaging with experts in the fields of biology and ethics can help us promptly understand the technical feasibility of the project and the ethical norms that need to be followed, including the ethical norms during the experimental process and the ethical issues involved in the final product.

Pharmaceutical companies (commercial feasibility)

We can categorize pharmaceutical companies into two types: those mainly producing traditional drugs (such as antibiotic manufacturers) and innovative pharmaceutical companies (producing nanobody drugs). We will consider the opinions of both types of companies. Both types of companies can provide us with information on product commercialization processes, process optimization, production cycles, etc. We also plan to attempt cooperation in technology research and development or production with other pharmaceutical companies. The cooperation methods include joint project applications, project advisors, etc. Additionally, innovative pharmaceutical companies, as commercial entities similar to our project, can provide us with experience in commercializing innovative technologies.

Regulatory authorities (market access feasibility)

During our project process, we need to promptly review the relevant requirements of the drug regulatory authority and communicate with the staff of the regulatory agency to obtain information on product market access regulations. As an important entity in the policy environment, the regulatory authority will provide important suggestions on the technical direction and feasibility of our core product, and may also offer ethical suggestions for our product. For example, whether the concept of our product conforms to the local cultural environment. In the later stage of the project, we hope to expand the overseas market, so communication with international drug regulatory authorities, such as FDA and EMA, is also extremely important.

Medical institutions and hospitals (clinical application)

Medical institutions and hospitals are among the final purchasers of our products and are also potential partners for us. Medical institutions may have reservations about our projects, but they can offer important opinions regarding clinical safety and market compliance, and will also help us gain a deeper understanding of the Helicobacter pylori treatment market. As a group that directly interacts with patients, they can indirectly provide patients' concerns about different treatment options.

Patient (Commercialization)

Patients are the end users of our products, and their opinions on our project are extremely important. Patients' attitudes towards the product may be positive, viewing it as a remedy for the shortcomings of traditional antibiotic therapy. However, there are also concerns regarding price, combined medication, and biological safety. Additionally, we also hope to understand the prevalence of related knowledge about Helicobacter pylori prevention among the patient population. We hope to enhance the prevention of Helicobacter pylori through designing relevant educational activities, thereby reducing the infection problem of Helicobacter pylori at its source.

Healthy Organization (Corporate Social Responsibility)

During the implementation of the project, we will take into account the fulfillment of social responsibilities. We hope to communicate with healthy organizations to promote activities for the prevention and control of Helicobacter pylori and popularization of synthetic biology education. In our subsequent practical activities, we also attempt to implement this concept.

3.2 Engagement

We communicated with these stakeholders through interviews and other means to understand their views and provide feedback to the project design. To protect their privacy, we use alphabetic identifiers (e.g., Patient-A) to represent those who do not want to reveal their real names.

3.2.1 Interview with Clinician (Dr. Li)

Personal Introduction: Dr. Li is a Chief Physician in the Department of Gastroenterology at Shanghai Tianyou Hospital. He has extensive experience treating Helicobacter pylori and offers valuable insights and suggestions on nanobody–probiotic combination therapy.

In this interview, Dr. Li Mingfeng highlighted key breakthroughs in the treatment of Helicobacter pylori, which provides valuable guidance for the nanobody–probiotic combination therapy program.

1. Helicobacter pylori Infection Rate and Distribution

According to Dr. Li, the Helicobacter pylori infection rate among adults in China remains high at 40-50%. The large population base of H. pylori infections in my country provides a clear market demand for the development of new treatment options. Notably, infection rates vary significantly across age groups and regions, suggesting the need for differentiated interventions in the development of prevention and treatment strategies.

2. Limitations of Antibiotic Treatment

Existing antibiotic treatment options face three major challenges. First, due to the growing problem of drug resistance caused by overuse of antibiotics, resistance rates to first-line drugs such as clarithromycin have exceeded 20%, directly reducing the effectiveness of traditional quadruple therapy. Secondly, the complex medication regimen (14-day course of treatment, multiple daily doses) seriously impacts patient compliance. Clinical data show that approximately 30% of patients fail to complete standard treatment. Most importantly, antibiotic treatment can severely disrupt the intestinal microbiome. Recent studies indicate that it takes 6-12 months for the gut microbiome to return to normal, during which time patients may experience various digestive symptoms.

3. Limitations of Nanobody Therapy

Nanobody–probiotic combination therapy still faces several key challenges: First, the estimated cost of a single course of treatment is 50% higher than that of traditional antibiotics, which may affect medical insurance coverage and patient acceptance. Second, clinical trial data for this project is still lacking, potentially presenting scientific and regulatory hurdles. Third, the optimal dosing regimen and synergy with probiotics (including dosing schedule and dosage ratio) requires systematic experimental research. Manufacturing quality control and cost optimization remain key issues in the industrialization of this technology.

3.2.2 Interview with Biochemistry Professor (Professor Han)

Personal Introduction: Professor Han is a professor in the Department of Biochemistry at Nanjing University of Chinese Medicine. He has published numerous papers on nanotechnology for tumor treatment and has provided numerous suggestions and perspectives on this project's nanobody–probiotic combination therapy.

1. Current Status of Helicobacter pylori Infection and Clinical Needs

According to epidemiological survey data provided by Professor Han Xin, the overall infection rate of Helicobacter pylori in China is 46.7%, showing significant regional disparity. The infection rate in rural areas (52.3%) is significantly higher than in urban areas (41.5%). Notably, the infection rate among young people aged 20–39 remains above 35%, and this group has higher requirements for convenient and safe treatment. Professor Han specifically emphasized that the penetration rate of existing diagnostic technologies (such as the ¹³C urea breath test) in primary healthcare institutions is less than 60%, which directly hinders early detection and treatment of infected individuals.

2. Clinical Pain Points Analysis of Existing Treatment Options

Research by Professor Han's team revealed core challenges facing current treatment options: First, the severe epidemic of antibiotic resistance. Monitoring data from 2023 showed a metronidazole resistance rate of 73.5% and a clarithromycin resistance rate of 28.7%. Secondly, the actual completion rate of standard bismuth-containing quadruple therapy is only 58.3%, primarily due to the complex dosing regimen (four times daily) and adverse drug reactions (32.6% incidence). More concerning, antibiotic treatment can cause a 40–50% decrease in the alpha diversity index of the gut microbiota, with beneficial bacteria such as Bifidobacterium taking 3–6 months to return to pre-treatment levels. The nanobody therapy mentioned in our approach can effectively circumvent the problem of antibiotic resistance, and using probiotics as a carrier can mitigate damage to the gut microbiota.

3. Progress and Challenges in the Development of Nanobody Combination Therapies

Although nanobody–probiotic combination therapy can effectively circumvent the problem of antibiotic resistance, the professor believes that this technology still faces significant challenges. First, their large-scale production cost is 4-5 times higher than that of traditional antibiotics, and the stability of nanobodies in the acidic environment of the stomach needs to be further improved. Combination regimens with probiotics still need to be optimized, and different bacteria have significant effects on efficacy. Experiments should determine which probiotics are most effective against Helicobacter pylori.

4. The Importance of Popularizing H. pylori Information

Professor Han pointed out that public awareness of H. pylori still needs to be improved, and our team should focus on promoting awareness of H. pylori prevention. To this end, our online campaign will primarily focus on popularizing H. pylori information and the project, such as its symptoms and detection methods. Offline promotional activities will emphasize the differences between this project and conventional treatments, ensuring a genuine understanding of the program. Public feedback will also be collected to ensure there are no misunderstandings or misunderstandings.

3.2.3 Interview with Regulatory Specialist (Dr. Wang)

Personal introduction: Dr. Wang is the founder, Chief Scientific Officer, and Chairman of the Board of Darts Pharma. He is also a professor at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences. He has extensive experience in innovative drug development and regulatory review.

During the interview, Dr. Wang provided valuable advice on the regulatory pathway, quality control, combination drug risks, and ethical considerations for using probiotics to deliver nanobodies against Helicobacter pylori.

1. Drug Approval Focus

Regulatory agencies focus on whether new antibiotics bring clear clinical benefits, especially if they address unmet medical needs. Safety is a basic requirement, and advantages in reduced side effects and better targeting are key for approval.

2. Approval Path for Probiotic Carriers

There is no precedent in China for a "probiotics + nanobody" drug. If classified as food, the strain must be listed in the official food ingredient catalog and cannot claim therapeutic effects. If classified as a drug, full preclinical and clinical trials are required. A challenge is that probiotics mutate quickly and current quality standards cannot fully control their stability, making regulatory approval more difficult.

3. Regulatory Mechanism for Nanobodies

Nanobodies follow a similar approval path to conventional antibodies. Regulatory review focuses on safety, efficacy, and clear mechanisms of action. If submitted alone as a drug ingredient, the pathway is relatively well-defined

4. Combination Therapy Approval

If applying as a combination therapy, two unapproved drugs cannot be submitted together. Preclinical studies must show no harmful interactions such as metabolic conflict, increased toxicity, or reduced efficacy. Supporting animal data is required.

5. Clinical Approval Process

From lab research to market approval usually takes about ten years. After process development, quality standards, and preclinical studies, an IND (Investigational New Drug) must be submitted. Clinical trials proceed through Phases I–III. Nanobody drugs require strict safety testing in rodents and non-human primates (such as monkeys) before human trials.

6. Ethical Approval

Ethics reviews are conducted by the clinical institution's ethics committee. If the product design is reasonable and avoids sensitive issues, ethical approval is usually achievable.

7. Public Awareness & Promotion

Drug promotion must follow academic channels and target professionals such as doctors. To increase influence, teams can publish academic papers or present at conferences, rather than marketing directly to the public.

3.2.4 Interview with Industry Executive (Mr. Ye)

Personal Introduction: Ye Mao is the R&D Director at Yipinhong Pharmaceuticals. In this interview, he shared his views on the company's business operations, the antibiotic market, the prospects of nanobody drugs, the differences between traditional and emerging therapies, as well as healthcare insurance policies, the regulatory approval of innovative drugs, and pediatric drug development.

1. The potential of nanobody drugs

Nanobodies offer precise targeting, can cross the blood-brain barrier, and are promising for diseases such as cancer. However, they face high production costs and complex manufacturing; slight process changes can cause batch failure. Globally, only a few nanobody drugs are approved, mainly for cancer.

2. Comparison of Traditional Antibiotics, Probiotics and Nanobodies

Antibiotics: Affordable and widely used, but overuse can lead to drug resistance, and they are ineffective against viruses and fungi.

Probiotics: Safe and suitable for long-term use (e.g., brands like "Mami Ai"), but their effectiveness in treating Helicobacter pylori alone is limited.

Nanobodies: Precision treatment is the future trend, but the cost is the biggest bottleneck. Director Ye gave an example: CAR-T cell therapy costs 1.2 million per injection, which is beyond the reach of ordinary people because the treatment plan is customized according to the patient's condition, resulting in such a high price.

3. Collaboration, Commercialization and Regulatory Prospects of Helicobacter Pylori Therapy

Pharma companies may purchase patents or co-develop drugs; licensing deals can be lucrative (e.g., $100M license later yielding $2B product). To enter national insurance, drug prices often drop sharply (e.g., from 3000 to 300 RMB) in exchange for higher volume. Governments support new drug R&D but review advanced tech like nanobodies strictly due to uncertain long-term risks.

The "probiotics + nanobody" model could reduce side effects of current quadruple therapy, but cost reduction is essential. Investment may be limited because H. pylori treatments are mature, and companies prefer unmet medical needs. Exceptions exist for fast-track drugs (e.g., cancer, rare diseases).

4. Pediatric Drug Development: Special Requirements and Challenges

Mr. Ye pointed out that the development of pediatric drugs is far more challenging than that of adult drugs. The dosage must be extremely precise - it is best to use drops rather than tablets. The taste of the medicine is also very important; children may refuse to take it or vomit if the medicine has an unpleasant taste. Safety standards are also more stringent because the liver and kidney functions of children are still developing, which makes them more susceptible to side effects.

He also pointed out that the blood-brain barrier in children has not fully matured, so special care is needed in terms of dosage and formulation. Usually, the dosage needs to be adjusted according to weight or body surface area. Children metabolize drugs faster, which requires more frequent administration. Moreover, the therapeutic window is narrower, and the recruitment of clinical trials becomes extremely difficult due to parents' unwillingness to have their children as test subjects.

To address these issues, Mr. Ye proposed some improvement measures, such as adding strawberry flavor to increase acceptability, developing liquid oral formulations rather than injections for pediatric cancer drugs, and adjusting the dosage to one-tenth or one-twentieth of the adult dosage.

3.2.5 Interview with Patient (Miss S.)

Personal Introduction: The interviewee is a high school student who was diagnosed with Helicobacter pylori infection through a urea breath test.

1. The drawbacks of antibiotic treatment

This patient was diagnosed with Helicobacter pylori through an exhalation test and was prescribed a 14-day course of Western medicine treatment, including amoxicillin, clarithromycin, and omeprazole. During the treatment period, she experienced various side effects, such as a bitter taste in the mouth and diarrhea. She described the entire treatment process as quite challenging, especially because she needed to take the medicine strictly according to the schedule every day, which was particularly inconvenient during travel or other unusual situations.

Despite these difficulties, the patient remained positive about treating Helicobacter pylori. She understood that this bacterium reproduces rapidly and requires timely medical intervention. She was aware of the risks of antibiotic resistance and knew that missing doses would reduce the treatment effect. She was interested in alternative therapies that could reduce the number of required medications and simplify the treatment process but also emphasized the importance of considering the potential side effects of new treatments.

2. Lifestyle changes, preventive measures and follow-up

After the diagnosis, this patient experienced social anxiety symptoms when dining with others. To address this issue, she confided in her condition to her friends and tried to avoid group meals to reduce stress. She believes that by educating the public about Helicobacter pylori and conducting regular health checks, the importance of Helicobacter pylori screening can be emphasized.

To prevent re-infection, she plans to focus on dietary hygiene and overall health management. She also intends to undergo follow-up tests after completing the treatment and incorporate Helicobacter pylori screening into her annual health check-up program.

3. Attitude towards nano-vaccines and price sensitivity

The patient expressed her willingness to try a nano-vaccine that does not require the use of antibiotics. Her main concern was the efficacy and safety of the drug. She pointed out that the average price of domestic drugs usually ranges from 200 to 400 yuan, while imported drugs tend to be more expensive. In her opinion, the pricing should be comprehensively considered based on necessity and dosage.

3.2.6 Interview with Patient (Miss A)

Personal introduction: The interviewee is around 30 years old and recovered through self-healing.

1. Recovery of Helicobacter pylori infection:

The patient mentioned that she still had irregular stomach bloating after treatment, which shows that the recovery period of Helicobacter pylori eradication is very long, and there is a certain possibility of complications in the future. It is very important to prevent Helicobacter pylori from the root.

2. Patients' understanding of treatment methods:

The patient has a full understanding of the risks of existing treatment methods, the side effects and drug resistance of antibiotics, which shows that her health literacy is high, and the patient may be more cautious in choosing treatment methods.

3. Prevention and expectations:

The patient believes that Helicobacter pylori should be included in the pre-employment physical examination, and the screening of Helicobacter pylori should be strengthened, prevention should be carried out in advance, and diagnosis and treatment should be carried out as soon as possible.

3.2.7 Interview with Patient (Miss B)

Personal introduction: The patient was first found to be positive for Helicobacter pylori during a physical examination in 2021, perhaps earlier, but the Helicobacter pylori test value was low and he did not care. However, when he was examined again in 2023, the value was too high, exceeding 7 times the reference value, and the patient finally decided to treat Helicobacter pylori. The cause of the patient's infection is not clear, but it is speculated that it may be caused by unsterilized tableware when dining or eating out when he was young.

This interview is an interview about the treatment experience of Helicobacter pylori patients. The meeting mainly revolved around the process of patients discovering infection, antibiotic treatment, and their views and expectations on probiotic nanoantibodies. The two sides also discussed the public's lack of knowledge about Helicobacter pylori and the direction of improvement.

1. Treatment

The doctor prescribed 4 drugs to treat Helicobacter pylori. During the treatment, the patient took a lot of drugs and antibiotics. The patient also mentioned that because the amount of medicine was large, it was particularly easy to miss it. Therefore, our probiotic nanoantibody therapy needs to be improved in terms of dosage, so as to reduce the possibility of omissions in patients when taking medicine and improve the cure rate of patients.

2. Expectations for new treatments

Patients hope that there will be treatments with shorter treatment cycles, fewer side effects, and no obvious drug resistance than antibiotics. In addition, patients also said that if the treatment can be permanent, they are willing to pay 10 times the price of antibiotic treatment.

3. Knowledge of Helicobacter pylori

Patients pointed out that people around them do not pay enough attention to Helicobacter pylori, and there are even problems of delayed treatment for positive patients. Failure to treat in time may aggravate the condition. They hope to strengthen the publicity of Helicobacter pylori.

3.2.8 Interaction with Peking University iGEM team

On July 28, 2025, Pylori Shield visited Peking University for an in-depth discussion with the igem team there. We first briefly introduced our project to the team and received numerous constructive suggestions.

The first suggestion was to consider the potential for drug resistance in the urease target, a potential issue for future public use. We will therefore address this concern in future experiments and attempt to address it.

The second suggestion was to consider the potential biological and environmental safety issues that may arise from the excretion of the nanobodies by patients. We will also consider this important factor in subsequent experiments.

The third area for improvement was about Peking University's WeChat official account. They have published several articles on gastrointestinal pathogens, such as Campylobacter jejuni and Vibrio cholerae. After discussion, our team agreed that this was a great idea: not only to educate people about Helicobacter pylori, but also to raise awareness of the various bacteria that can harm our gastrointestinal tract. Furthermore, the igem team mentioned in their WeChat official account that they have also published several popular science articles on synthetic biology, which we find very worthwhile to learn from.

The fourth suggestion is commercial. When promoting our product, we can mention the disruption that traditional triple and quadruple therapy causes to the gastric environment. This is because antibiotics indiscriminately kill all intestinal bacteria, and disrupt the normal bacterial environment. This can lead to side effects and cause pain and discomfort for patients. In contrast, our product, nanoantibodies, can precisely target Helicobacter pylori. It not only addresses the drug resistance issue of traditional antibiotics, but also ensures that the normal gastric flora is not affected. The probiotics included in the product can even enhance the survival of these bacteria.

The conclusion includes patient, commerce, regulation, technique and other aspects. We summarize the result of the survey and interaction, and feed them back into the project design.

1-(Background) High Helicobacter pylori Infection Rates in China

Helicobacter pylori is one of the most common chronic bacterial infections worldwide and has maintained an infection rate of 40% to 50% among adults in China. In rural areas, the infection rate even exceeds 50%, reaching 52.3%. This demonstrates that the prevention and treatment of Helicobacter pylori is a critical issue in contemporary society. Our project hopes to alleviate this challenge and contribute to society.

2-(Technical Advantages) Traditional Treatment Options for Helicobacter pylori Infection Have Certain Limitations

"quadruple antibiotic therapy" is the current mainstream treatment and has exposed numerous problems in clinical application.

In the interview, both Director Li and Professor Han pointed out the challenges of drug resistance and long recovery periods faced by traditional quadruple antibiotic therapy. Director Li cited the continued rise in antibiotic resistance, severe damage to gastric flora, and low patient compliance. He also emphasized that current treatment methods can cause persistent side effects in some patients, increasing the failure rate of treatment. Professor Han further supplemented relevant data, noting that the resistance rate to the antibiotic metronidazole is as high as 73.5%, while the completion rate for standard treatment is only 58.3%, less than 60%.

We will thoroughly reflect and propose corresponding measures for the three major issues raised by them. First, regarding the increasing resistance rate, we will explore alternatives to traditional treatments and plan to implement antibody-based therapies to address resistance. Second, broad-spectrum antibiotic therapy can severely disrupt the gastrointestinal microbiome. To mitigate this, we will explore the possibility of targeted therapies to significantly reduce the disruption to the normal microbiome. Finally, we will further explore solutions to alleviate low patient compliance and increase patient willingness to complete the full course of treatment by shortening the treatment cycle. In summary, the issues and challenges raised by experts regarding current traditional treatments serve as a reminder and motivation for us to further explore solutions or supplementary options to provide alternatives for patients who are unable to undergo traditional treatment.

3-(Patient Perspective) Antibiotic Treatment: Complex Dosing and Inconvenience

Interviews with three patients revealed that traditional antibiotic treatments present certain inconveniences in practice. The first patient interviewed stated that during her 14-day quadruple antibiotic therapy, she needed to take multiple medications daily. This treatment approach not only requires strong self-discipline, but also can lead to interruptions during travel or other disruptions to her daily routine, compromising treatment effectiveness. Furthermore, the patient reported experiencing side effects such as a bitter taste in the mouth and diarrhea, which further increased the physical and mental stress and burden, leading to significant anxiety and resistance during treatment. Meanwhile, the second patient interviewed, despite being aware of the dangers of Helicobacter pylori, chose not to pursue medication, opting instead to wait and recover on her own. This further demonstrates the persistent concern about side effects.

As Professor Han pointed out in the interview, the current treatment completion rate is only 58.3%, meaning that nearly half of patients fail to fully follow their doctor's treatment plan. The complexity of the treatment process directly reduces treatment compliance and undermines patients' trust in and acceptance of medical advice. Therefore, our project design places particular emphasis on convenience. We hope to leverage probiotic delivery systems and nanobodies to optimize traditional treatment regimens, which typically require continuous administration of multiple medications, into simpler, more consistent regimens. This will help reduce treatment stress for patients and enhance their experience and effectiveness.

4-(Public Perspective) Insufficient Public Awareness of the Risks of Helicobacter pylori

Experts have reported that the general public lacks knowledge about H. pylori prevention and awareness of its harmful effects. Furthermore, questionnaire data indicates that public awareness of H. pylori is incomplete, particularly regarding its dangers and causes. This highlights the importance of public education about H. pylori.

5-(Regulatory Perspective) Complex Clinical Approval Process with No Approved Cases to Date

In our interview with Dr. Wang, we gained an in-depth understanding of the current Chinese drug regulatory requirements for the approval of new probiotics and nanobodies. Dr. Wang pointed out that while probiotics have widespread applications in food and healthcare, there is currently no precedent for successfully approving them as live bacterial drugs within the drug approval system in China. The biggest challenges facing these drugs are their lack of stability and controllability. Probiotics are prone to mutation and rapid reproduction during production and storage, making it difficult to maintain consistent quality and stability between batches. This makes it difficult for regulators to establish clear approval standards. Therefore, while some companies have attempted to advance live bacterial drugs, their progress remains stuck at the approval stage and has not yet entered the clinical stage.

In contrast, Dr. Wang expressed a relatively optimistic view on the regulatory and approval path for nanobodies themselves. He pointed out that as functional antibody fragments, nanobodies have a highly similar R&D and application process to traditional antibody drugs. Numerous R&D and clinical trials have already been conducted both domestically and internationally, with some products having received clinical approval or even marketing authorization, demonstrating the maturity of regulatory mechanisms in this field. Therefore, the feasibility of nanobodies as new drugs entering the clinical stage is recognized by the regulatory system. To address regulatory challenges, our team has implemented practical measures in its design: First, we are initially selecting probiotic strains already listed in the food ingredient catalog to circumvent regulatory hurdles; second, we are minimizing modifications to the bacteria itself in functional design to avoid transgenic red lines; third, we are focusing on batch-to-batch consistency and intend to control strain activity and quantity through a freeze-dried powder process to enhance product stability.

Although the regulatory pathway is not yet mature, through initial process specification and standardization efforts, we hope to lay the foundation for subsequent project applications and gain experience for similar treatment strategies.

6-(Business Perspective) Two Possible Paths to Commercialization

During our conversation with Director Ye, we learned that there are currently two common paths for innovative drugs to enter the market. The first is to collaborate with large pharmaceutical companies through patent licensing or co-development, with the companies leading the drug registration, clinical trials, and market launch processes. The second is to independently pursue the product, initially launching it as a functional food or health supplement, and then considering drug registration or medical insurance inclusion after accumulating sufficient data.

Each path has its advantages and disadvantages. While a partnership model can leverage pharmaceutical companies' resources and experience to expedite the approval process, it also means ceding control of the project, and early-stage pharmaceutical companies' willingness to invest remains uncertain. While medical insurance approval can reduce patient costs and expand the market, it presupposes that the product must first complete the full approval process, demonstrate efficacy, and accept a significant price reduction. Director Ye gave an example: some innovative drugs must reduce their price from 3,000 yuan per box to 300 yuan to gain medical insurance approval. This sacrifices profits in exchange for increased sales, and for a startup team, this approach presents excessive risks and resource pressures.

Based on the project's current maturity and resource availability, our team has decided to prioritize the second path: entering the market with a functional product positioning. We plan to focus on "regulating gastric flora and optimizing the intestinal microbiome," leveraging the availability and safety of probiotics to launch our first-generation product and achieve initial market success. Simultaneously, we will gradually accumulate product usage data, user feedback, and safety assessment reports, and consider transitioning to a drug approval path when conditions are ripe. This option represents a slower but more steady approach, and we hope to provide a more acceptable alternative to those who are troubled by traditional treatments in this gentle and pragmatic way.

1. Technology Advancement

Based on expert feedback and existing literature, we plan to continue optimizing the stability of nanobodies in gastric acid and explore different probiotic encapsulation methods (such as microencapsulation and liposomal encapsulation) to improve delivery efficiency. Furthermore, we will strive to extend the viability of probiotics and minimize losses during transportation and storage by selecting appropriate encapsulation methods.

In order to address the risk of urease resistance raised by the Peking University igem team, we plan to test multi-target nanobody combinations in subsequent experiments to mitigate the possibility of target mutations leading to reduced efficacy.

2. Public Engagement & Education

Based on the areas of public awareness identified in the survey (transmission routes, prevention methods, and understanding of nanobodies), we plan to launch a series of online educational articles. The team has already conducted educational activities on Rednote and our official WeChat account regarding how to prevent Helicobacter pylori and plans to continue to address other areas of public awareness. Furthermore, we will prioritize these issues identified in our research in our education activities and incorporate them as much as possible into the design and implementation of these activities (see the education session for details). Regarding public feedback on the new technologies involved in our project, we plan to regularly collect public feedback on this technology throughout the implementation process and incorporate this feedback into subsequent technical and promotional optimization.

3. Regulatory & Ethical Considerations

In accordance with expert advice, we will initially enter the market with a functional product combining food-grade probiotics and nanobodies, accumulate safety and efficacy data, and explore a drug registration path once the technology matures. We will prioritize probiotic strains already listed in the food ingredient catalog and minimize modifications to the strain genome to ensure easier product development in terms of regulatory compliance and public acceptance.

To address potential environmental emission risks and safety issues, we plan to design a controlled inactivation mechanism for the probiotics and conduct environmental degradation experiments to ensure their safety.

4. Commercialization Pathway

In terms of commercialization, based on preliminary cost estimates (see the Entrepreneurship section for details) and interviews, we decided to implement R&D and sales independently as our primary commercial path. However, considering the risks of this approach, We have designed a backup plan. Once the product reaches initial maturity, We plan to negotiate joint development or patent licensing with pharmaceutical companies with experience in nanobody or probiotic R&D.

We have fully considered the consumer feedback from the questionnaire regarding acceptable price ranges and drug forms (such as capsules and powders). We will continue to optimize our production processes and raw material supply chain to ensure that product prices align with the purchasing power of our target users, and we have decided to use capsules as the final product.