RectomeDy FotoZymogen: A Light-Controlled Probiotic Therapy for Postoperative Colorectal Cancer

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide, and postoperative recurrence remains one of its most critical clinical challenges. Despite major advances in surgery, chemotherapy, and immunotherapy, 30% of patients still experience recurrence, largely due to microscopic residual lesions that cannot be completely removed.

The RDFZ-China 2025 project, RectomeDy FotoZymogen, presents an innovative synthetic biology solution that integrates engineered probiotics, optogenetic control, and hardware-assisted light delivery.

Our goal is to transform post-surgical cancer management by introducing a precise, localized, and biosafe probiotic therapy, activated only under red light.

The system consists of two synergistic components:

1. An engineered probiotic strain (EcN) that colonizes tumor sites, secreting dual therapeutic molecules under red-light activation;
2. A magnetically controlled red-light suppository, a miniaturized medical hardware designed to safely deliver light to the colorectal region.

Together, they form a smart, controllable therapy that reduces systemic toxicity, improves targeting precision, and enhances patient comfort.

This business document explores the market need, technological potential, commercial pathway, and long-term vision of this innovation, paving the way for its translation from research to real-world application.

1. Unmet Clinical Need

Postoperative recurrence of CRC presents a serious clinical problem. Traditional chemotherapies often fail to eliminate microscopic lesions and cause significant side effects such as nausea, hair loss, and bone marrow suppression.

Immunotherapies and targeted drugs offer better specificity but remain expensive and limited to certain patient groups.

There is an urgent need for a localized, cost-effective, and controllable therapeutic strategy that minimizes side effects while maintaining high precision.

RectomeDy FotoZymogen addresses this gap by:

• Delivering treatment only where it’s needed — inside the colorectal cavity;
• Allowing external control using a non-invasive red-light trigger;
• Using safe probiotic bacteria (E. coli Nissle 1917) already used clinically as a dietary supplement.

2. Target Market and Customers

Our potential market can be divided into three main segments:

Segment	Description	Needs & Opportunities
Primary Healthcare Market	Hospitals, oncology centers, and gastroenterology departments	Seek adjunct therapies that can reduce recurrence risk and hospital costs
Biotech & Pharma Industry	Biotherapeutic and synthetic biology companies	Need modular, patentable therapeutic systems for future pipelines
End-User Segment	CRC patients and their families	Desire effective, safe, and less painful treatment options

Based on our preliminary survey (see original data in user study), medical professionals show high acceptance (8/13) of probiotic-based suppository treatment, while patient families demonstrate moderate openness pending safety data and physician endorsement.

Thus, our initial commercialization should focus on B2B cooperation with hospitals and biotech firms, before direct patient-facing implementation.

3. Market Drivers

• Rising CRC Incidence: China alone reports over 550,000 new CRC cases annually (National Cancer Center, 2024).
• Growing Acceptance of Microbiome Therapies: The global microbiome therapeutics market is projected to exceed USD 2.5 billion by 2030.
• Advancements in Synthetic Biology and Optogenetics: Increasing demand for precise, tunable gene-expression tools.
• Shift Toward Personalized and Minimally Invasive Medicine: Clinicians are increasingly receptive to targeted, patient-specific therapies.

4. Competitive Landscape

Category	Chemotherapy	Immunotherapy	RectomeDy FotoZymogen
Target Precision	Low	High	High
Side Effects	Severe	Moderate	Minimal
Treatment Delivery	Systemic	Systemic	Localized (rectal)
Cost	High	Very High	Moderate
Controllability	None	Partial	Fully Controlled (Light-Inducible)
Safety	Cytotoxic	Autoimmune Risks	Engineered Biocontainment (PBAD-MazF)

Our solution does not aim to replace existing therapies, but rather to complement them — serving as an adjunct, post-surgery treatment to prevent recurrence safely and affordably.

5. Validation Through Customer Research

Our field survey included 13 key stakeholders (medical professionals, patient families, and potential end users).

Key Insights:

• Top Concerns: Mutation out-of-control (13 mentions) and immune/allergic responses (13 mentions).
• Decision Drivers: Clinical efficacy data (15 mentions) and treatment safety (15 mentions).
• Improvement Suggestions: Reducing side effects, improving precision, and ensuring expandability of clinical research.

These findings emphasize that biosafety assurance and clinical data transparency will be the most decisive factors in public and institutional adoption.

1. Biological System: Engineered Therapeutic Probiotic

Our therapeutic platform is built on E. coli Nissle 1917 (EcN) — a safe probiotic strain used for decades in clinical probiotics (e.g., Mutaflor®).

It is engineered with a modular synthetic biology circuit comprising four key functions:

Module	Function	Core Part
Tumor Targeting	INP-HlpA fusion anchors bacteria to CRC cells via HSPG recognition	BBa_25PXJQ2S
Light Control	NETMAP red-light inducible promoter system enables temporal precision	BBa_259UHA9L, PadC, BphO
Therapeutic Payloads	Coa (coagulase) blocks tumor vasculature; PD-L1 nanobody triggers immune reactivation	BBa_256O7C4S, BBa_25GADZ5E
Biosafety	PBAD-mazF system ensures self-destruction upon external induction	BBa_K1096002 (modified)

Mechanism:

Once delivered into the colorectal cavity, the bacteria colonize the post-surgical microenvironment. Upon external red-light exposure from the hardware device, therapeutic proteins are expressed locally. After therapy, the PBAD-mazF system can be induced to terminate bacterial survival, ensuring biosafety.

2. Hardware System: Magnetically Controlled Red-Light Suppository

To activate the engineered bacteria in situ, we designed a biomedical hardware prototype — a magnetically controlled red-light suppository capable of precise, localized illumination.

Design Highlights:

• Compact Form Factor: Less than 1 cm diameter; comfortable for rectal use.
• Hall Magnetic Switch: Allows wireless activation, eliminating the need for complex electronics.
• Sealed Biocompatible Casing: Multi-layer epoxy encapsulation ensures safety and durability.
• Sustained Operation: Low-power design supports continuous red-light output for 24 hours.

Function:

Patients insert the capsule post-surgery; when the magnetic switch is triggered, it emits 660 nm red light to activate the NETMAP system in probiotic cells, initiating therapeutic expression.

This hardware not only serves the current project but also acts as a modular optogenetic device for other synthetic biology applications, including biosensors and drug delivery systems.

3. Integration of Bio & Hardware

The integration between our engineered bacteria and smart hardware creates a closed-loop therapeutic platform:

• Biological precision ensures spatial targeting;
• Hardware control ensures temporal activation;
• Inducible kill-switch ensures post-treatment clearance.

This integrated approach transforms synthetic biology from a lab concept into a clinically viable, patient-centered therapy system.

1. Product Form and Value Proposition

RectomeDy FotoZymogen is not a single product — it is a platform that combines:

1. Therapeutic Probiotic (Biological Component) — the engineered E. coli Nissle 1917 with controllable therapeutic functions.
2. Smart Hardware Device (Physical Component) — the magnetically controlled red-light suppository for external activation.

The combined system creates value through:

• Precision Therapy: Red-light control minimizes off-target effects.
• Safety: Multi-layer biosafety design (PBAD-MazF + ecological containment).
• Patient Comfort: Non-invasive delivery method.
• Cost Efficiency: Low production cost compared to immunotherapy or biologics.

2. Commercialization Pathway

Our commercialization strategy will follow a phased model, transitioning from academic research to industrial application.

Stage	Time Frame	Milestone	Description
Stage I: Preclinical Validation	2025–2026	In vitro & animal experiments	Validate safety, controllability, and therapeutic efficacy in model systems.
Stage II: Clinical Partnerships	2026–2028	Hospital pilot program	Collaborate with oncology departments for controlled human trials.
Stage III: Industrial Collaboration	2028–2030	Technology transfer	Partner with biotech firms to optimize strain production and hardware manufacturing.
Stage IV: Regulatory & Market Entry	2030–2032	CFDA/FDA approval & commercialization	Launch as an adjunct therapy for CRC recurrence prevention.

This stepwise approach minimizes risk while building credibility through validated data and partnerships.

3. Revenue Model

We propose a hybrid revenue system:

B2B Licensing Model:

• Licensing the engineered probiotic strain, genetic circuit designs, and optogenetic control modules to biotechnology and pharmaceutical companies for adaptation into their therapeutic pipelines.

Medical Device Sales:

• Manufacturing and distribution of the red-light suppository hardware as a Class II medical device for hospitals and clinics.

Research Kit Distribution:

• Developing educational and research versions of our system (non-clinical EcN strain + red-light hardware) for universities, high schools, and bio-labs, promoting synthetic biology education.

4. Cost Structure

• R&D and Laboratory Operations: Strain engineering, genetic verification, and hardware prototyping.
• Manufacturing: Bioreactor fermentation for EcN, medical-grade encapsulation for hardware.
• Regulatory Compliance: Preclinical testing, biosafety certification, and ethics documentation.
• Marketing and Partnerships: Hospital collaborations, academic conferences, and outreach.

Our model emphasizes scalability and modularity — once the optogenetic platform is approved, it can be repurposed for other cancer types or gastrointestinal diseases with minimal re-design.

1. Technical Risks

Risk	Description	Mitigation Strategy
Mutation or Genetic Instability	Engineered strains may accumulate mutations affecting control or safety.	Utilize redundant biosafety modules (PBAD-MazF + containment), perform continuous sequencing checks.
Uncontrolled Expression or Leakage	Basal expression could lead to premature toxin release.	Characterized PBAD promoter ensures tight repression; validated through OD600 growth curve tests.
Hardware Malfunction	Possible overheating or light output instability.	Waterproof encapsulation, magnetic switch failsafe, repeated endurance testing.

2. Ethical and Regulatory Risks

• Biosafety Compliance: The project strictly follows iGEM Safety Committee guidelines — all components either belong to the whitelist or have been reviewed by the committee.
• Public Acceptance: Synthetic biology remains unfamiliar to many; we mitigate this through transparent communication, HP education, and clinician endorsement.
• Ethical Oversight: Patient autonomy and informed consent are emphasized during clinical testing stages.

3. Market and Operational Risks

• Adoption Barrier: Physicians and patients may hesitate without clear efficacy data → conduct robust preclinical trials and publish results.
• Cost Barrier: High device costs may limit accessibility → optimize hardware for low-cost batch production using biocompatible polymers.
• Competition: Existing immunotherapies dominate → position RectomeDy as complementary, not competing, therapy.

1. Academic Collaborations

We aim to continue partnerships with:

• CAU-China – for synthetic biology education co-development and safety testing.
• MPA-USA – for collaborative CRC therapeutic design.
• BNDS-China – for modeling and public communication.

These collaborations demonstrate the feasibility of international academic partnerships in advancing real-world applications.

2. Hospital and Clinical Cooperation

Future clinical-stage development requires partnerships with:

• Oncology Departments of major hospitals (e.g., Peking Union Medical College Hospital).
• Gastrointestinal Research Institutes for model testing and biosafety assessment.

These partnerships will validate clinical safety, dosage, and patient response profiles.

3. Industrial and Corporate Partners

Potential industry partners include:

• Biotech Companies: For strain production and gene therapy adaptation.
• Medical Device Manufacturers: For hardware refinement and certification.
• Venture Funds in Synthetic Biology: To scale manufacturing and distribution.

1. Environmental and Social Responsibility

• Biocontainment Commitment: All engineered strains contain triple-layer kill-switch systems, ensuring zero environmental risk.
• Recyclable Hardware Materials: The red-light suppository casing is designed from recyclable, biocompatible materials to reduce waste.
• Ethical Innovation: Promote public literacy in synthetic biology and ensure transparent communication of risks and benefits.

2. Expansion Beyond CRC

The same framework can be adapted to:

• Other Gastrointestinal Tumors: Such as gastric or pancreatic cancer.
• Microbiome Engineering: For inflammatory bowel disease (IBD) and other chronic gut disorders.
• Smart Drug Delivery: Using light-controlled bacterial systems for precise payload release in different organs.

3. Educational Continuity

RDFZ-China commits to publishing open-access educational resources, including our:

• Optogenetic hardware design files;
• Safety training manuals for student labs;
• Modular genetic design guides.

This ensures that future iGEM and student teams can build upon our foundation.

1. Economic Value

If successful, RectomeDy FotoZymogen could:

• Reduce hospital readmission rates for CRC patients by up to 20%;
• Lower treatment costs by substituting expensive biologics with self-producing therapeutic probiotics;
• Stimulate interdisciplinary innovation across synthetic biology, electronics, and medicine.

2. Societal Benefits

• Improve post-surgery quality of life for millions of CRC survivors;
• Raise awareness of biosafety and responsible biotechnology use;
• Inspire young scientists to pursue translational research bridging biology and engineering.

Looking ahead, RDFZ-China envisions a world where therapy is programmable, personalized, and safe.

We will expand RectomeDy FotoZymogen into a universal platform for optogenetic medical treatments, collaborating with hospitals, biotech companies, and policymakers to establish a sustainable industrial chain — from engineered probiotic production → hardware fabrication → clinical implementation.

Our long-term goal is to make synthetic biology-driven therapies accessible worldwide, while fostering public trust, ethical responsibility, and a deeper understanding of biotechnology’s potential to heal.

This business proposal is not just a commercial plan — it is a blueprint for transforming synthetic biology from laboratory innovation into practical, human-centered healthcare.

Through open collaboration, ethical responsibility, and scientific excellence, RectomeDy FotoZymogen aims to become a pioneer in controllable probiotic therapeutics.

Analysis of the original survey questionnaire：