Why Commercialization is Essential

As the MPA-USA team, we firmly believe that only through commercialization can our project truly benefit patients. The incidence of colorectal cancer (CRC) among young populations is rising rapidly, while existing therapies are associated with severe side effects, high costs, and limited accessibility.

Our solution leverages engineered probiotic EcN to site-specifically synthesize neoeriocitrin in the gut, combined with acidic microenvironment induction and a dual biosafety system, achieving a more precise and safer adjunct therapy.

The necessity of commercialization is reflected in several aspects:

• Scalable and standardized production: It transforms the challenges of low yield, batch variability, and high cost in traditional plant extraction into biological fermentation-based scalable and standardized production, significantly reducing costs and ensuring product consistency.
• Regulatory and clinical integration: Only via commercialization can we complete regulatory compliance, clinical validation, and insurance reimbursement pathways, enabling engineered probiotics to enter hospitals and insurance systems, thus alleviating financial burdens for families.
• Widespread adoption and iterative improvement: Commercialization allows project outcomes to be implemented and adopted by the public, forming a research–application–improvement cycle. Through this cycle, we can not only promote innovation adoption but also iteratively refine technology, further reduce costs, and develop safer and more effective therapies.

Commercialization is not just a bridge for translating research into application, but also a guarantee for responsible innovation. For MPA-USA, our goal is to transform breakthroughs in synthetic biology into practical, affordable clinical solutions, giving more patients real-world access to new hope.

MPA-USA Neoeriocitrin Probiotic Powder is an innovative adjunct therapy and preventive product for colorectal cancer (CRC). Its chassis strain is the widely used and safe Escherichia coli Nissle 1917 (EcN). Through synthetic biology techniques, key enzymes including VvRHM, UGT73B2, and Cm1,2RhaT are introduced to achieve efficient in situ synthesis and release of neoeriocitrin in the gut.
Neoeriocitrin is a natural citrus-derived flavonoid with notable anti-inflammatory, antioxidant, and immunomodulatory properties, which can improve the intestinal microenvironment and inhibit tumor cell growth.

The product uses an acid-sensitive CadBA promoter, which specifically induces key enzyme expression in the acidic tumor microenvironment, achieving precise targeting. This is combined with a dual biosafety system (pBAD-arabinose inducible and pCspA-low temperature inducible, both driving MazF) to ensure controllable in vivo activity and environmental safety.

Our solution integrates targeting, efficacy, and safety, offering CRC patients a scalable, affordable, and novel therapeutic option.

Potential Customers

Based on urgency of need and decision-making power, we classify potential customers into three categories:

Primary Customers: Colorectal Cancer (CRC) Patients

• They are the direct end-users of the product.
• After surgery, chemotherapy, or radiotherapy, they have a strong demand for adjunct therapies with fewer side effects and lower financial burden.
• Goal: Improve quality of life and long-term recovery.

Secondary Customers: Patients’ Families & High-Risk Populations

• Family members bear economic and caregiving responsibilities, and thus care about cost and convenience.
• High-risk populations (those with family history, inflammatory bowel disease, or young adults) seek scientific and affordable preventive interventions.
• Significance: Represents an important future expansion market.

Tertiary Customers: Medical & Health Institutions

• Includes oncology hospitals, gastroenterology departments, rehabilitation centers, insurance companies, and health management platforms.
• They determine whether the product can enter clinical pathways or reimbursement systems, and are key partners for large-scale adoption and public accessibility.

Unmet Needs

There are still gaps in current therapies:

• Patient Level: Existing treatments have severe side effects, leading to reduced quality of life.
• Family Level: Families face heavy economic and time burdens and lack low-cost alternative solutions.
• Public Level: There is insufficient awareness of early-onset CRC and the scientific value of Naringenin.
• Physician Level: Clinicians urgently need long-term adjunctive or preventive therapies that balance efficacy and safety.

If you would like to learn more about our interview content, please click the link to view the Human Practice.

Our Response

Based on the feedback above, our product utilizes engineered probiotics to synthesize Naringenin in situ within the gut, combined with an acid-sensitive inducible expression system and dual biological safety switches. This approach addresses the limitations of traditional extraction methods—low yield, high cost, and inconsistent quality—providing safe and effective adjunct therapy for primary patients, reducing the economic burden on families, and offering a scalable and affordable pathway for healthcare institutions and high-risk populations.

Feasibility Analysis – Market Analysis

Market Potential

Early-onset CRC is continuously rising, and long-term complications pose heavy economic burdens; there is a clearly increasing clinical and patient demand for milder, long-term auxiliary and preventive solutions. Traditional extraction of neohesperidin from dried tangerine peel suffers from “low yield, high cost, and batch variability” bottlenecks. We replace extraction–purification with in situ synthesis in EcN—featuring scalable fermentation and lyophilization, providing better quality control .

The global CRC treatment market (TAM) is approximately USD 12.5 billion; in parallel, the microbiome/probiotic therapy sector was about USD 95 million in 2022, expected to reach “multi-billion” scale by 2030. The market is small but grows fast with high barriers to entry, suitable for differentiated approaches.

TAM、SAM、SOM

TAM（Total Addressable Market）

Total global CRC-related spending: surgeries, chemo/radiotherapy, targeted therapy, immunotherapy, and all adjunct treatments, totaling USD 12.5 billion. Our solution falls under “CRC auxiliary and preventive therapy,” within this total.

SAM（Serviceable Available Market）

Defined by “microbiome/probiotic therapies in CRC scenarios.” Based on a 2022 base of USD 95 million, projected at 30–40% CAGR, SAM ≈ USD 800–1,200 million by 2030.

SOM（Serviceable Obtainable Market）

Focusing on the U.S. as the initial market, targeting three segments:

• Postoperative or post chemo/radiotherapy adjuncts
• Recurrence risk management
• Early-onset CRC under 40 years

Conservative Scenario: Early adoption rate in the U.S. 0.3–0.5%, per-course price USD 2–4k (6–9 months), 2–4k users/year → annual revenue USD 5–15 million. Baseline Scenario: Adoption ~1%, per-course price USD 3–5k, 8–12k users/year → annual revenue USD 30–60 million. Optimistic Scenario: After multi-center evidence and reimbursement negotiations, adoption 2–3%, 20–30k users/year → annual revenue USD 100–300 million.

Why “U.S. First”

The U.S. offers a relatively clear R&D and clinical evaluation pathway for live biotherapeutic products (LBPs). Key opinion leader (KOL) networks, patient organizations, and real-world evidence (RWE) generation mechanisms are well-established. The team can simultaneously explore early commercialization paths via insurance and out-of-pocket channels, and initiate pilot studies with integrated delivery networks (IDNs), oncology specialists, and gastroenterology specialists. The U.S. also has a mature cGMP ecosystem for fermentation–lyophilization–cold chain–quality control, facilitating standardization and traceability ( Feasible).

Scalability

Our scalability is not only reflected in increased production capacity but also in the gradual expansion from technology to application, from patients to the public, from a single molecule to a platform pipeline. This provides a strong scalability advantage, mainly derived from two aspects: technical reproducibility and application extensibility.

Technical Level: Natural transition from lab to industrialization

Currently, neohesperidin depends on traditional Chinese medicine extraction, suffering from raw material limitations, high cost, and batch variability. By using engineered E. coli Nissle 1917 to synthesize neohesperidin in situ, we bypass these extraction constraints (Innovative). The core logic of our project is “fermentation → purification → formulation”, which aligns closely with current pharmaceutical and probiotic industrial production models. This means we can leverage existing cGMP fermentation and lyophilization facilities to scale production. With increasing fermenter size and standardized downstream processes, unit costs will rapidly decrease, enabling long-term affordable accessibility (Scalable, Feasible).

Application Level: Expansion from adjunct therapy to health management

• Phase 1: Target CRC patients for postoperative adjunct therapy and post chemo/radiotherapy recovery, emphasizing the value of reducing side effects and improving quality of life (Feasible).
• Phase 2: As clinical evidence accumulates, extend to early intervention for high-risk populations, such as young individuals with a family history or chronic inflammation, providing a long-term, affordable preventive solution (Feasible, Scalable).
• Phase 3: Based on the same synthesis platform, further expand to other natural products and cancer-related indications, forming an iterable product pipeline (Scalable, Innovative).

Sustainability and Regulatory Support During scaled production, our dual-suicide system (pBAD + pCspA → MazF) significantly improves regulatory acceptability, providing safety assurance for industrialization and internationalization (Feasible). Additionally, probiotic products already have successful commercialization precedents (e.g., Mutaflor®), making our product pathway practically feasible (Feasible).

Inventiveness

MPA-USA has demonstrated unique innovation in the field of adjuvant therapy for colorectal cancer. Our core innovation lies in combining the biosynthesis of the natural product neohesperidin with an engineered probiotic platform, overcoming the limitations of traditional herbal extraction, which often suffers from low yield, high cost, and batch variability. By reconstructing the synthetic pathway in Escherichia coli Nissle 1917, we achieved, for the first time, in situ biosynthesis of neohesperidin in the intestinal environment, providing patients with a more stable and affordable therapeutic source, and offering a new model for the modernization of natural products.

Furthermore, our expression control strategy is equally innovative. Traditional engineered probiotics often face the challenge of precise release, whereas we introduced the acid-sensitive promoter CadBA, enabling the key enzymes of neohesperidin to be expressed only in the acidic tumor microenvironment, thus achieving “on-demand production and localized release”. This strategy enhances therapeutic targeting and avoids systemic side effects, representing a significant breakthrough in current probiotic drug delivery models.

In terms of biosafety, we designed a dual suicide system (pBAD + pCspA → MazF). This not only allows users to manually trigger bacterial self-destruction when necessary, but also ensures automatic inactivation under low environmental temperatures, minimizing the risk of escape. This dual design, balancing human control and environmental triggers, demonstrates our original thinking in synthetic biology safety.

Looking ahead, our innovation extends beyond a single product to a platform potential. This synthesis and delivery framework can be expanded to more natural products and functional molecules, providing a sustainable and iterative R&D pathway for cancer prevention, adjuvant therapy, and even chronic inflammation management. This molecule-to-platform approach gives our project a unique competitive advantage in both scientific breakthroughs and commercial implementation.

During the exploration of product commercialization, the MPA-USA team interviewed venture investors to gain professional advice on business models, market entry points, and financing strategies.

In these interviews, we introduced the product design concept and business plan to the investors. They provided specific and constructive advice on market positioning, cost control, promotion channels, and potential competitors, and indicated their willingness to provide support at the appropriate stage of development.

Below are images from our interviews with investors, which served as important references for shaping the commercialization pathway.

Timeline and Milestones

We have formulated a phased development plan for 2-year, 5-year, and 10-year stages. This stepwise approach ensures that the project progresses from laboratory research to clinical application and eventually to market implementation.

2-Year Plan

• Complete laboratory optimization and validation of the engineered strains, ensuring the neohesperidin biosynthetic pathway is stable and effective, while enhancing the safety of the dual suicide system.
• Conduct small-scale lyophilized formulation pilot production in partner laboratories or incubator platforms, exploring the feasibility of production processes.
• Initiate patent applications and intellectual property (IP) strategy, laying the foundation for future industrialization.
• Engage in preliminary science communication and outreach with patient groups and medical associations to establish product awareness.

5-Year Plan

• Advance preclinical validation and early-phase clinical trials, accumulating safety and efficacy data.
• Establish partnerships with pharmaceutical companies or probiotic enterprises to form an industry alliance and enter the market incubation stage.
• Focus on high-burden CRC markets in the U.S. and China, targeting young patients and preventive populations as core customers.
• Gradually expand into the health management and functional food sector, developing composite products such as NMN + neohesperidin and probiotic nutritional supplements.

10-Year Plan

• Build the product into a platform pipeline, extending beyond neohesperidin to develop other anti-inflammatory and antioxidant molecules (e.g., NMN, GSH) on the same probiotic chassis, covering multiple areas including cancer prevention, anti-aging, and gut health.
• Establish a global commercial footprint, leveraging pharmaceutical collaborations and insurance coverage, promoting CRC adjuvant therapy into standard medical practice.
• Achieve dual B2B and B2C growth, serving both hospitals, clinics, and professional channels, as well as entering the consumer market for nutritional supplements and preventive products.

Business Model

Our business model is designed as a combination of B2B and B2C, evolving in phased stages:

Early Stage (2–5 years) – B2B Focus

• Target hospitals, clinics, and pharmaceutical companies as primary customers.
• Sell probiotic lyophilized formulations (clinical adjuvant therapy products) through B2B partnerships.
• Provide raw material products (neohesperidin lyophilized powder) to pharmaceutical and health supplement companies.

Mid Stage (5–10 years) – C2C Expansion

• Expand to consumer-facing products while ensuring safety and efficacy.
• Develop oral probiotic formulations for consumers, targeting cancer prevention and gut health management as functional products.
• Distribute through e-commerce, pharmacies, and health food channels.

Long-Term Stage (10+ years) – Platform Pipeline & Dual Revenue Streams

• Sell proprietary end products (probiotic capsules, combined nutritional supplements) directly to consumers.
• Supply engineered bacterial raw materials and patent licensing to other pharmaceutical and health supplement companies.
• Achieve a diversified revenue model combining products + raw materials + IP licensing.

Team Execution and Resources

Organizational Structure组织架构

Core Team (MPA-USA): Composed of a high school research team, organized into Wet Lab (experimental group), Dry Lab (modeling and data group), Human Practice (HP group), Business, and Art & Design (promotion and design group). The team has clear division of labor, possessing both scientific research capabilities and market and social communication skills.
Advisors and Research Mentors: Experts in molecular biology, synthetic biology, medicine, and intellectual property, ensuring academic rigor and research compliance.

External Collaboration Resources：

During our Human Practice process, we interviewed a wide range of stakeholders. Their feedback has provided important references for our current project design and optimization and will serve as the foundation for iterative dialogue in the project’s continuous development, providing long-term support for future improvement and expansion.

• Hospital oncologists → Provide clinical needs and application feedback
• Traditional medicine/natural product experts → Validate the scientific value of Chenpi/neohesperidin
• Biopharmaceutical companies and lyophilization factories → Provide production and formulation process consultation
• Investors and insurance companies → Evaluate market pathways and payment system feasibility

Execution Capability

• Completed the construction and validation of the neohesperidin biosynthetic pathway, and established the dual suicide safety system, demonstrating scientific feasibility.
• Through interviews and surveys, established clear user personas and market needs.
• Possess business plan drafting and financial planning capabilities, and have communicated with investors to preliminarily validate commercial feasibility.
• Have interdisciplinary team collaboration experience, capable of forming a closed loop across scientific, social, and commercial dimensions, ensuring the project is “doable and achievable”.

Financial and Funding Plan

Cost Structure

• R&D Costs: gene synthesis, plasmid construction, laboratory consumables, cell culture, and validation (~40%)
• Production Costs: strain fermentation, lyophilization processes, quality testing, packaging design (~30%)
• Human Resources: research personnel, marketing, clinical consultants, and legal support (~20%)
• Other Expenses: intellectual property applications, travel, and promotion (~10%)

Funding Stage Plan

• Angel Round (1–2 years): Primarily for research validation and small-scale pilot production, estimated funding $500,000–$1,000,000
• Series A (3–5 years): For preclinical studies and early clinical trials, and expanding production capacity, estimated funding $5,000,000–$8,000,000
• Series B (5–10 years): For market promotion, international registration, and channel expansion, estimated funding >$20,000,000

Break-Even Expectation

• Expected to reach break-even in years 6–7, as clinical adjuvant therapy products enter the market and insurance coverage.
• Long-term revenue growth relies on a dual B2B + B2C model (hospital channels + consumer market).

Patent Strategy

To ensure legal protection of project outcomes and future commercialization potential, we plan to file relevant patents in the U.S. Establishing an IP barrier not only protects core technology from imitation but also facilitates future industrialization and external collaborations.

Below is our preliminary patent application table:

Patent ID	Type	Description	Scope of Protection
P1	Invention Patent	Neohesperidin biosynthetic pathway in engineered E. coli Nissle 1917 (combinatorial expression of VvRHM, UGT73B2, Cm1,2RhaT)	Protects the complete metabolic circuit design and its application scenarios
P2	Invention Patent	Acid-sensitive induction system (key enzyme expression driven by CadBA promoter)	Specific regulatory mechanism targeting the acidic microenvironment of CRC tumors
P3	Invention/Utility Patent	Dual biosafety suicide system (pBAD + pCspA driving MazF)	Safety design scheme for engineered bacteria in in vivo and ex vivo environments
P4	Application Patent	Application of engineered probiotic lyophilized formulations in CRC prevention and treatment	Protection for productization and formulation process applications

Risk Analysis

To ensure a smooth transition from R&D to clinical application and market implementation, we conducted a comprehensive risk analysis.

The table below presents the potential risks at each stage and the corresponding mitigation strategies.

Stage	Risk	Possible Solutions
Proof of Concept	Engineered bacteria are effective under laboratory conditions, but show insufficient effect in simulated gut or animal models	Collaborate with research institutions; conduct animal studies and preclinical validation; optimize bacterial metabolic pathways and delivery methods
Test Phase	Insufficient subject recruitment, poor patient compliance, or high variability in product efficacy	Collaborate with hospitals for clinical pilots; provide subsidies and health management services to improve compliance; dynamically optimize formulation and dosage
Regulatory	Probiotic + neohesperidin combination may face complex and lengthy approval processes	Consult regulatory experts; prepare GRAS/IND documentation; adopt stepwise registration strategy (initially as health supplement, then transition to medical use)
Marketing	Low public awareness and skepticism toward engineered probiotics + Chenpi components	Conduct science communication and outreach; obtain endorsement from doctors/nutritionists; design targeted marketing strategies for CRC patients and high-risk populations
Scaling Up	Factory conditions or production processes may be insufficient to maintain yield and cost advantage	Collaborate with established fermentation companies; optimize lyophilization protectants; use contract manufacturing (CMO) to ensure stable supply

CRC Engineered Probiotic Project – Risk & Exit Strategy Analysis

Exit Strategy

Given the uncertainties in the healthcare and biotechnology markets and the high regulatory barriers for clinical application, MPA-USA must design a flexible exit strategy to minimize risks while ensuring the long-term value of the CRC engineered probiotic project.

Horizontal M&A

• Collaborate with or be acquired by a large pharmaceutical or nutrition company with an existing probiotic or functional food portfolio.
• This partnership can provide critical funding, advanced manufacturing capabilities, and established clinical trial networks.
• Leveraging the partner’s global brand influence and market channels, our engineered probiotics can gain faster recognition among CRC patients and the public, enhancing credibility as an adjuvant or preventive therapy.

Licensing

License the engineered E. coli Nissle strains and neohesperidin biosynthetic pathway to leading biotech or probiotic companies. This approach enables large-scale product promotion by leveraging the partner’s expertise in mass fermentation, regulatory registration, and global distribution. Meanwhile, MPA-USA can generate stable revenue through licensing fees and royalties, reducing independent commercialization risks and financial pressure, while realizing project value conversion.

Team Skills and Capabilities

MPA-USA is composed of a group of high school students who are enthusiastic and responsible, with diverse cultural backgrounds and life experiences. Team members demonstrate professional abilities in synthetic biology experiments, modeling, and data analysis, as well as unique talents in business planning, design, outreach, and interdisciplinary collaboration. This diverse background and individuality endows the team with strong creativity and execution capability.

Through interdisciplinary division of labor and collaboration, team members contribute their strengths at different stages：

• Wet Lab Group drives probiotic construction and neohesperidin pathway validation
• Dry Lab Group supports experimental optimization through research and analysis
• Business Group leads market research, surveys, and interviews, facilitating product commercialization pathways
• Design & Outreach Group creates product packaging, promotional materials, and demonstration videos, giving the project clear branding and communication impact

Additionally, the team benefits from collaboration with university laboratories and medical experts, gaining technical guidance and clinical feedback. Details of individual members’ expertise and specialization can be found on our Team page.

Stakeholders

To ensure the project addresses real needs, MPA-USA has conducted a systematic identification and categorization of relevant stakeholders. We adapted Mendelow’s Matrix, evaluating groups along influence–interest dimensions. Through communication with diverse stakeholders, we not only validated the problem definition but also identified unmet needs, allowing continuous optimization of research directions and practical approaches.

Category	Our Actions	Our Expectations
Customers	Conduct in-depth interviews with patients and families to investigate real needs, focusing on side effects, cost, and convenience	Expect them to try and adopt our solutions, provide continuous feedback, and help optimize the product
Specialists	Interview TCM practitioners, researchers, and doctors, integrating traditional knowledge and modern science to validate therapy mechanisms	Provide academic support and clinical feedback to enhance the scientific rigor and feasibility of the project
Partners	Establish collaborations with university labs and companies, share resources, and explore production and commercialization pathways	Offer technical, industrial, and financial support, accelerating product implementation
Regulators & Public	Consult regulatory advisors to clarify compliance pathways; work with media and science communicators to increase public awareness	Help us progress through approvals, improve social acceptance, and expand science communication impact

If you would like to learn more about our interview content, please click the link to view the Human Practice.

Recognizing the rising incidence of colorectal cancer (CRC), especially among younger populations, and the limitations of existing treatments such as surgery, radiotherapy, and chemotherapy, the MPA-USA team is committed to leveraging synthetic biology to develop a safe, accessible, and effective probiotic therapy. Based on research and stakeholder feedback, we anticipate the following long-term impacts on health, society, and the environment:

1、Improving Quality of Life

Current CRC treatments often involve severe side effects such as nausea, fatigue, and immune suppression. Our engineered E. coli Nissle can produce neohesperidin with anti-inflammatory and antioxidant properties, potentially alleviating treatment side effects and improving daily quality of life for patients. This aligns with the Sustainable Development Goal of “Good Health and Well-being”.

2、Economic Accessibility

Traditional therapies are expensive, imposing a financial burden on families.

Using microbial fermentation technology, we significantly reduce the production cost of neohesperidin, making preventive or adjuvant therapy more affordable. This contributes to reducing economic pressure on CRC treatment and supports the SDG of “Inclusive and Sustainable Economic Growth”.

3、Public Health Awareness

Surveys reveal limited public awareness of early-onset CRC and preventive measures. Through health education and outreach activities, our project aims to raise societal awareness of gut health, cancer prevention, and functional probiotics, encouraging proactive health management.

4、Environmental Sustainability

Unlike many high-energy chemical synthesis methods, our approach uses sustainable microbial biosynthesis to produce active molecules. The engineered bacteria incorporate a dual biosafety switch, preventing environmental release and ensuring ecological safety. This supports the SDG of “Life on Land” and demonstrates the potential of synthetic biology in green healthcare.

5、Potential Adverse Impact: Low Social Acceptance

The public still has concerns about “genetically engineered bacteria”, and some patients or families may worry about safety and ethical risks, potentially affecting market adoption. Mitigation: We will leverage Human Practice interviews with doctors, patients, and regulators, continue science communication and transparent engagement, and use patent protection and regulatory compliance to build trust. Prior to market entry, the product will be presented in standardized lyophilized probiotic formulation, increasing user acceptance.

Considering these long-term impacts, we believe the CRC engineered probiotic project is not only a scientific innovation but also a redefinition of cancer care: reducing side effects, lowering costs, improving public awareness, and safeguarding environmental safety.

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[2] Fletcher, T., Thompson, A. J., Ashrafian, H., & Darzi, A. (2022). The measurement and modification of hypoxia in colorectal cancer: overlooked but not forgotten. Gastroenterology report, 10, goac042.

[3] Foundation Inc. (2023, September 21). TAM SAM SOM: What it means & how to calculate it. Foundation Marketing Lab.

[4] Market.us. (2023). Global colorectal cancer therapeutics market size, share, growth report [2023–2033]. Market.us.

[5] Grand View Research. (2023). Microbiome therapeutics market size, share & trends analysis report: Forecasts 2023–2030. Grand View Research. Retrieved from

[6] Dharwadkar, P., Zaki, T. A., & Murphy, C. C. (2022). Colorectal Cancer in Younger Adults. Hematology/oncology clinics of North America, 36(3), 449–470.