The Unmet Problem: No Single Biomarker Defines Cancer
A recurring challenge in oncology is that no single biomarker perfectly distinguishes cancer cells from healthy tissue. Most markers are imperfect because they are:
- Shared with healthy cells → e.g., alpha-fetoprotein (AFP), long studied in HCC, is often elevated in hepatitis and cirrhosis as well as cancer, reducing its specificity (Gupta et al., Ann Intern Med, 2003).
- Not universally present → e.g., glypican-3 (GPC3) is overexpressed in ~70-80% of HCC tumors, but not all, and low levels can appear in benign liver lesions (Moek et al., American Journal of Psychology, 2018).
- Heterogeneous within tumors → Even within the same tumor, different regions or clones may express different biomarkers, and these profiles can shift over time as the cancer evolves or responds to therapy (Dagogo-Jack and Shaw, Nature Reviews in Oncology, 2018)
Why does this matter? For patients, therapies triggered by a single biomarker carry real risks. If that biomarker is also present in healthy tissue, the treatment can cause dangerous off-target toxicity. If only part of the tumor expresses it, or if expression changes over time as the cancer adapts, the disease can slip through and return. This is why so many promising treatments fall short in clinical trials: a single marker just can't capture the complexity of cancer.
Where LiRA fits. LiRA tackles this challenge by listening for multiple cancer signals at once. Instead of switching on for a single imperfect biomarker, it only activates when a precise combination of biomarkers is present. This design gives treatments the chance to focus only on cancer cells, while also covering residual tumor cells that might otherwise escape, all while leaving healthy tissue unharmed.
Our General Solution: Combinatorial RNA Logic
Instead of discarding imperfect biomarkers, LiRA uses them together to create a more dependable trigger for treatment.
How it Works: LiRA detects RNA transcripts inside a cell and connects them through logic rules. For example, an AND gate can be programmed so that the system only activates when two or more biomarkers are present together. When this condition is met, LiRA produces an output protein that could either be a research reporter in the lab or a therapeutic molecule in a clinical setting. If the condition is not met, the system remains inactive.
Illustration of a two-input LiRA circuit: the therapeutic protein is produced only when both inputs are present.
To further improve safety and specificity, LiRA uses a split protein strategy. Instead of producing a full protein in response to a single input, each input drives expression of only half of the protein. The two halves are harmless on their own, but when both are expressed in the same cell, they assemble into a functional protein. This ensures that all required biomarkers must be present simultaneously before the therapeutic effect can occur.
A single marker can be noisy, but the requirement for multiple inputs along with the split protein design greatly increases specificity and lowers the chance of false activation.
Beyond our immediate project, LiRA functions as a platform technology. Because both the sensors and the split protein outputs can be reprogrammed, the same system can be adapted to other cancers or diseases where multiple markers are available. This makes LiRA not just a one-off therapy, but a generalizable approach to targeting complex diseases.
Why HBV-HCC as Our Therapeutic Focus
LiRA could be applied to many cancers, but we chose Hepatitis B virus-driven hepatocellular carcinoma (HBV-HCC) because it combines a high global burden with a biology that highlights the strengths of our system.
- Global impact. Liver cancer is the 3rd leading cause of cancer death, with ~800,000 deaths each year. Chronic hepatitis B affects >250 million people worldwide and drives 40–50% of HCC cases.(Rumgay, Journal of Hepatology, 2022)
- Clinical gap. Even after curative treatment, recurrence rates reach 50-70% within five years. When relapse occurs, five-year survival drops to ~30%. (Wang et al., The Oncologist, 2020)
- Logic fit. HBV-HCC cells often carry integrated HBV DNA, which produces viral transcripts absent from healthy hepatocytes (Yeh et al., Cell Mol Gastroenterol Hepatol., 2023). These can be paired with endogenous HCC markers (e.g., GPC3, AKR1B10) as inputs for LiRA's AND gate.
- Novelty. We are the first to apply RADAR RNA-sensing to a viral application. In HBV-HCC, parts of the HBV genome randomly integrate into the host DNA, producing viral transcripts that differ from patient to patient. By comparing data across many samples, we identified regions that are consistently retained. LiRA uses these conserved viral transcripts, together with cancer markers, as reliable inputs—showing the system's flexibility beyond conventional biomarkers.
By starting with HBV-HCC, we target a disease where patients urgently need better options, while also demonstrating LiRA's unique ability to handle viral integration events. Thus, we offer a proof of principle for future applications of LiRA in other cancers and infectious diseases.
Our Products
Product #1: Logic-gated RNA therapeutic for HBV-driven HCC
A therapeutic design delivered by liver-tropic LNPs that activates only when two signals are present inside a cancer cell: an HBV integration-derived transcript and an HCC marker (e.g., GPC3/AKR1B10). When both inputs are detected, LiRA expresses or reconstitutes a split therapeutic protein (e.g., IL-2 variant) to kill tumor cells; otherwise it stays off.
Unique Value Proposition of LiRA's HBV-HCC Therapeutic:
LiRA aims to deliver higher tumor specificity by requiring two independent intracellular signals and adds a second safety layer by using split-protein reconstitution, creating a therapy that is designed to spare healthy tissue while remaining programmable enough to retarget to other virus-linked or multi-marker cancers.
Product #2: LiRA Toolkit (Research-Use Only) for Labs
An off-the-shelf kit for running dual-input intracellular RNA logic (AND) in mammalian cells. Labs choose two RNA targets, plug them into LiRA, and read out a built-in reporter (e.g., GFP/luciferase) or a model split-therapeutic output. All in vitro.
What's in the box:- Two pre-validated RNA input sensor constructs are included and can be retargeted to your chosen RNA sequences.
- You can select a reporter output (such as green fluorescent protein or luciferase) or a model split-therapeutic output for in-cell testing.
- Standard Operating Procedures (SOPs), quality-control documents, and a no-cloning workflow enable a transfection-to-readout timeline of a few days.
- The optional LiRA-Designer guide helps you choose input pairs and produces build specifications.
- Technical support and example datasets from benchmark cell lines are provided to validate and calibrate your experiments.
- Lets researchers test multi-biomarker logic without weeks of custom cloning.
- Generates published case studies and user data that de-risk the therapeutic path.
- Creates early revenue and partnerships while clinical development proceeds.
Unique Value Proposition of LiRA's RUO:
LiRA gives researchers true in-cell logic control with two RNA inputs and modular outputs, delivered through a no-cloning, days-to-data workflow that can be reprogrammed for new targets without rebuilding the entire system.
Stakeholders and Collaborations
IHP Integration
LiRA's direction was shaped by clinicians, patient advocates, researchers, and biotech practitioners we engaged throughout the project (see our Integrated Human Practices page for full interviews, quotes, and artifacts). From early workshops with THICA Taiwan (delivered in Mandarin to reach the HBV community) to a 350-response survey that went viral on campus social media (~1.5K upvotes on Fizz), we consistently heard the same message: people want safer, more selective options that do more than detect risk.
What patients and advocates asked for. Conversations with leaders like Dr. Jacki Chen (THICA) and community participants underscored fear of liver cancer, underdiagnosis and stigma, and frustration with toxic or late options. Their input pushed us to keep LiRA off in healthy tissue and design for clear, patient-centered communication about safety and intent.
What clinicians and experts told us. Hepatology/oncology experts (e.g., Dr. Mindie Nguyen, Dr. Robert Gish) advised beginning in late-stage, refractory HBV-HCC with hard safety endpoints and measurable biomarker readouts. Mechanism discussions with Dr. Charles Rice and Dr. Jianghong Rao led us away from antibody outputs toward cytokine/split-protein strategies, and delivery guidance supported liver-tropic lipid nanoparticles. This feedback directly shaped LiRA's dual-input logic (HBV integration RNA + HCC marker) and our initial clinical plan.
What we changed because of this. We pivoted from an early diagnostic to a therapeutic that acts only when two intracellular signals are present; we committed to a Research Use Only toolkit first to generate data and partnerships before trials; and we framed our first-in-human study around late-stage HBV-HCC with explicit safety and target-engagement measures.
For names, dates, longer quotes, survey dashboards, and workshop details, see our Integrated Human Practices page.
Official Partnership with RADAR Therapeutics: Educational Kit
We are collaborating with RADAR Therapeutics to develop an educational kit that introduces RNA logic systems to students. This kit is separate from our LiRA research toolkit, but the collaboration benefits both teams because we share the same goals: making the technology affordable and scalable while ensuring it is reliable and reproducible. We are working directly with RADAR's education group and have already begun planning the kit together.
What does the educational kit look like? The kit uses a yeast-based system with a simple visual on/off readout, designed to fit within a single class period. It meets BSL-1 safety standards, making it appropriate for classroom use. RADAR plans to distribute the kit through established education suppliers like Bio-Rad Explorer and Fisher Science Education, which are channels that schools already trust and use. This distribution approach keeps costs manageable for schools while allowing RADAR to focus on creating high-quality educational content.
How does this collaboration help LiRA? Developing an education kit requires us to build standardized components, write clear standard operating procedures, and implement quality checks that work reliably for any user, including students and teachers who may have limited lab experience. These requirements push us to create documentation, lot-release criteria, and packaging standards that are rigorous enough to survive real-world classroom conditions. Everything we learn from making the education kit robust and reproducible will transfer directly to our RUO toolkit manufacturing. If the system works consistently in classrooms with varying skill levels and equipment, we can be confident it will perform well in research labs.
Why is this collaboration significant? First, this is an active partnership with a company team, not just a side project. RADAR specifically asked us to help develop a kit they intend to launch commercially. Second, this represents our first step toward building a standardized, production-ready system with demonstrated feasibility. The manufacturing pipeline we develop for the education kit will make it much easier to scale up production for a lab-grade RUO toolkit.
Why is moving into research labs important? While education kits help build familiarity with RNA logic technology, getting LiRA into research labs is where the technology becomes truly useful at scale. Research labs provide faster iteration cycles, access to diverse cell lines for testing, and opportunities for early publications and case studies. Lab users also form a community that helps refine protocols, identify edge cases, and stress-test our support systems. By sharing open protocols and example datasets, we lower the barrier for new research groups to adopt LiRA. Feedback from core facilities and principal investigators working on translational research will guide us in deciding which RNA inputs and therapeutic outputs we should prioritize for our commercial product.
What is our current progress? We have agreed on the core design: a yeast demonstration system with visible on/off readouts. We have outlined the structure for teacher materials and standard operating procedures, and we have defined the basic quality control requirements. Our next steps include supporting small classroom pilots with teacher reviewers to test the kit in real educational settings, collecting data on reliability and reproducibility, finalizing the bill of materials, and applying the same quality control standards and documentation practices to pilot lots of the LiRA RUO toolkit.
Mentorship from Pheast Biosciences
We connected with Pheast Biosciences through Shefah Qazi, an employee at the company. We pitched LiRA to her and proposed a potential collaboration between our project and Pheast. The idea resonated with the team, and the CEO and founder were impressed enough to offer us weekly mentorship meetings. These sessions provided guidance on both the experimental aspects of our project and our entrepreneurship and commercialization strategy, giving us practical advice from experienced industry professionals.
Our entrepreneurship subteam went to Pheast and successfully pitched LiRA to one of their employees, Shefah Quazi.
The company also invited our entire team for an extensive tour of their facilities. We got to see their complete pipeline, from early research through production, which gave us valuable insight into how a biotech company operates at scale. During the visit, we networked with employees across different departments and established strong connections. The validation and enthusiasm we received from Pheast was encouraging; their positive response to LiRA suggests that other biotech companies will likely be receptive to our products as well.
Expert Interviews and Pivot Points
From the beginning, we sought feedback from people with experience in entrepreneurship, biotech ventures, law, and translational research. In fact, many of the experts we spoke with are iGEM alumni! While these interviewees were not our eventual end-users, their perspectives were critical in shaping LiRA’s strategy.
Based on their input, we pivoted from a purely therapeutic focus to a two-phase strategy:
1. Academic Toolkit → short-term product for synthetic biology labs, generating revenue and adoption data.
2. Therapeutic Development → long-term path targeting HBV-HCC, supported by regulatory planning and eventual partnerships.
Each conversation below revealed key insights that refined LiRA's commercialization strategy. Click to explore what we learned and how we adapted.
Interview Date: August 4th, 2025
Background: Dr. Jovian Yu is a Medical Director at AbbVie, where he works in clinical development and medical affairs for oncology programs. His pharmaceutical industry perspective provided critical insight into how major companies evaluate early-stage platforms like LiRA for commercial and regulatory viability.
Key Takeaways:
(1) Dr. Yu emphasized that FDA oncology programs typically begin in advanced, refractory patient populations who have exhausted standard treatments. This regulatory convention exists because novel therapies with uncertain risk-benefit profiles are most ethically justifiable in patients with limited alternatives. We incorporated this guidance into LiRA's clinical development plan, targeting late-stage, treatment-refractory HBV-HCC patients for initial trials before potentially expanding to earlier-stage disease.
(2) Dr. Yu recommended developing a Target Product Profile (TPP), a strategic document defining the product's key characteristics including indication, patient population, dosing, safety profile, and clinical endpoints. His advice prompted us to begin mapping LiRA's target indication, proposed endpoints, and differentiation from existing therapies.
(3) While majority of HBV-HCC cases occur in sub-Saharan Africa and Eastern Asia due to high chronic HBV prevalence, Dr. Yu noted the U.S. represents the optimal initial market given its established regulatory infrastructure, clear reimbursement pathways, and concentration of NCI-designated cancer centers for clinical trial execution. We structured our commercialization strategy accordingly: launch therapeutically in the U.S. first, then expand to high-burden regions through partnerships and differential pricing models.
Interview Date: August 5th, 2025
Background: Dr. Joshua Makower is the Yock Family Professor of Medicine and Bioengineering at Stanford, where he founded the Biodesign program. He serves as Founder and Executive Chairman of ExploraMed, a medical device incubator that has created ten companies since 1995, and holds over 300 patents and patent applications. His expertise in medical innovation, commercialization, and IP strategy provided crucial guidance for positioning LiRA effectively.
Key Takeaways:
(1) Dr. Makower emphasized that applying existing technology to novel applications is patentable and advised filing provisional patents promptly. He noted "we live in a first-to-file world" with a one-year grace period from first public disclosure. For LiRA, even though it builds on RADAR, our novel application to viral integration markers represents patentable innovation. He stressed documenting what is distinctly new—particularly our conserved HBx transcript identification and dual-input viral-plus-cancer logic—and ensuring proper inventor attribution.
(2) Dr. Makower identified significant gaps in our TAM-SAM-SOM analysis. With approximately 42,000 HCC cases annually in the U.S. and 50% HBV-attributable, he noted LiRA's modular design could address broader markets. Using $28,000/month pricing for targeted cancer therapies, he estimated a U.S. TAM of $1 billion, expanding to $5 billion globally. He advised focusing on TAM rather than forcing artificial SOM calculations, and identifying actual limiting factors like diagnosis rates or delivery constraints.
(3) He affirmed LiRA "looks really promising as a therapeutic approach" and advised validating the scientific approach in small animal models as the critical next step.
Interview Date: August 6th, 2025
Background: Michael Becich serves as Chief Executive Officer of Cache DNA. He holds degrees in Bioengineering and Mathematical & Computational Sciences from Stanford University and an MS/MBA in Biotechnology from Harvard Business School. His experience spans roles as Lead Data Scientist at Octave Bioscience, Bioinformatics at Illumina, and Synthetic Biology at NASA, bringing diverse perspective on translating research tools to clinical applications.
Key Takeaways:
(1) Becich emphasized conducting both top-down and bottom-up market analyses. For top-down, he advised understanding all disease subtypes and geographies to trace how the global 300 million chronic HBV patients funnel down to our lead candidate population, including total therapeutic spend in this space. For bottom-up, he recommended multiplying current standard-of-care costs by patient numbers to validate market estimates with concrete data rather than assumptions.
(1) Becich noted that addressing HBV-HCC represents a "noble goal" targeting a patient population that has seen declining therapeutic innovation in recent years. He advised painting a story using previous successful drugs in similar delivery contexts as precedent for LiRA's viability. He emphasized that LiRA's unique advantage (our dual-input specificity enabling precise tumor targeting) should be prominently featured and repeatedly reinforced throughout our presentation.
Interview Date: August 7th, 2025
Background: Taylor Sihavong is President and Co-Founder of Code.X, an international tech education nonprofit bringing programming and design education to youth in under-resourced and refugee communities. Featured in Forbes 30 Under 30 for Education, she is a Stanford d.school graduate who previously worked as Senior Product Designer at Pear Therapeutics, Change Healthcare, and Agathos, specializing in U.S. healthcare and ultra low-cost solutions for the global south.
Key Takeaways:
(1) Sihavong advised against the nonprofit route if we envision diverse revenue streams, noting that biotech development requires sustainable business models. She emphasized that free products lack perceived value and organizations should charge customers to remain viable. Nonprofits can work when grants and donations cover additional costs and pricing adjusts to local economies, but the approach depends heavily on target countries and desired organizational control.
(2) For LiRA's U.S. beachhead market, Sihavong recommended starting with relapsed/refractory patients, or those who have exhausted standard treatments. She noted that therapies don't necessarily need to drastically improve survival rates to provide value; improving quality of life in patients' final months represents meaningful clinical benefit and a viable initial market entry point. This aligns with regulatory expectations for novel oncology therapies and provides a clearer path to demonstrating therapeutic value.
Interview Date: August 13th, 2025
Background: Nghi Nguyen is Vice President of Corporate Development at AnaptysBio, a clinical-stage biotechnology company developing immune cell modulators for autoimmune and inflammatory disease. As a Stanford iGEM founder and alum with degrees in Biology (BS) and Management Science (MS), he provided both entrepreneurial and pharmaceutical industry perspective on LiRA's development.
Key Takeaways:
(1) Nguyen emphasized that our problem statement needed more clinical detail to resonate with investors and partners. He suggested specifying disease progression timelines—how long chronic HBV takes to develop into HCC—and providing deeper context on disease state to establish urgency. He also recommended researching companies currently treating HBV-caused HCC to better position LiRA's differentiation within the competitive landscape.
(2) For TAM calculation, Nguyen advised starting with the 800,000 patients receiving immunotherapy globally, then taking a subset representing advanced-stage disease (approximately 50%, yielding roughly $40 billion market potential). We followed this approach.
(3) Nguyen suggested researching clinical trial costs by examining publicly traded companies with HCC studies, as they must report quarterly R&D expenditures. He also recommended reviewing published papers that summarize average costs for each trial phase. Understanding these benchmarks helped us develop credible budget projections and identify appropriate funding targets.
Interview Date: August 13th, 2025
Background: Dr. Marc Van Eden is Vice President of Corporate Development at Zymo Research, a life sciences company that provides innovative nucleic acid purification technologies and research tools. With a PhD in biochemistry and postdoctoral training in molecular virology, he is a member of the American Association for Cancer Research, American Chemical Society, and RNA Society. Zymo's mission focuses on making high-quality, simple-to-use research products, operating entirely on earned revenue without investor funding.
Key Takeaways:
(1) Dr. Van Eden strongly cautioned against immediately pursuing clinical trials, noting the immense regulatory hurdles, high failure rates, and the risk of "putting all eggs in one basket with a lot of unknowns." Instead, he advocated launching LiRA first as a Research Use Only (RUO) tool, a research consumable that scientists can use to explore multi-input RNA logic systems in their own labs. This approach offers multiple strategic advantages: it generates early revenue without requiring FDA approval, builds connections and partnerships across academia and industry, demonstrates the technology's utility and versatility through real-world applications, and creates a sustainable funding stream to support longer-term therapeutic development. His advice was most influential in causing us to reshape our commercialization strategy.
(2) Building on the RUO concept, Van Eden proposed exploring a partnership with Professor Gao to create a spin-off entity focused on RADAR as a research platform with prepackaged, plug-and-play target libraries. By making the system accessible to researchers without extensive molecular biology expertise, we expand the potential user base dramatically. Through licensing agreements, we generate revenue for the Gao lab while enabling other scientists to discover new applications and markets, which in turn creates additional IP and funding opportunities. This model mirrors Zymo's fully organic growth philosophy of bringing in money from strategic partners rather than relying on investor pressure.
Interview Date: August 15th, 2025
Background: Dr. Glenn Foulds is a patent attorney specializing in chemistry, biotechnology, and pharmaceutical intellectual property. Before transitioning to law, he had a distinguished scientific career as a postdoctoral researcher and startup scientist developing small molecule drugs, nucleic acid technologies, and engineered peptide biomolecules. With 15 years of patent prosecution experience, he applies his deep R&D background to protect innovative platform technologies and drug candidates, particularly in areas like PROTAC and LYTAC degraders, engineered proteins, and therapeutic applications.
Key Takeaways:
(1) Foulds confirmed that LiRA's use of known biomarker sequences in novel combinations is patentable. He explained that both composition of matter (the construct itself) and method of use (the mechanism and application) can be claimed. Taking known components and putting them together for a new use, particularly when the combination is non-obvious and serves a specific disease target, creates novelty. Even naturally occurring sequences become patentable when placed in an unnatural pharmaceutical context like LiRA's logic-gated construct.
(2) Since LiRA is a Stanford-owned invention (as we are students), Foulds advised coordinating with OTL to file the initial provisional, ideally having them invest in a proper patent application through their partner firm rather than just submitting slides. He noted potential complexities around "double patenting" when company-owned next-generation IP overlaps with Stanford IP, but emphasized this shouldn't concern us immediately. He recommended enlisting Professor Gao to clarify the RADAR licensing situation and explore whether Stanford would support filing for LiRA as complementary technology.
(3) Foulds stressed finding the broadest defensible application of LiRA's technology when drafting claims. This means not limiting ourselves unnecessarily to specific biomarkers or disease states if the underlying platform principle applies more widely. Strong patent applications define broad-to-narrow scope through multiple claims, providing maximum flexibility for future applications while maintaining a defensible core innovation.
Interview Date: August 18th, 2025
Background: Eileen Lee is a Senior Licensing and Strategic Alliances Manager at Stanford's Office of Technology Licensing, bringing experience in technology transfer and licensing from previous positions at UCSF and the Salk Institute. She managed the original RADAR patent filings for the Gao Lab, making her uniquely positioned to advise on LiRA's IP landscape.
Key Takeaways:
(1) Lee explained that patent applications must satisfy three statutory requirements: novelty (never disclosed before), non-obviousness (findings are not simply stitched together from existing knowledge), and utility (usefulness, though this is rarely the limiting factor). Our ability to patent LiRA depends entirely on the scope of the existing RADAR platform patent. If specific applications, sequences, or biomarker combinations weren't outlined in the original Gao Lab filing, those elements could potentially be patentable under a species/genus framework, where the broad platform is the genus and our specific application is a novel species.
(2) Lee emphasized a critical distinction: patentable and licensable are different concepts. Even if we secure a narrow patent on our specific HBV-HCC application, we still need freedom to operate within the broader RADAR platform, which is exclusively licensed to RADAR Therapeutics. This means we would require a sublicense from RADAR Therapeutics to commercialize any therapeutic application, and such sublicenses are not guaranteed, depending entirely on whether the licensee is willing to grant one. This clarification fundamentally shaped our understanding of LiRA's commercialization constraints.
Interview Date: August 19th, 2025
Background: Theresa Sievert is a Senior R&D/Product Development Engineer at Tracey Technologies and Stanford iGEM alum. Her experience in product development and commercialization strategy provided practical guidance on strengthening LiRA's market analysis and go-to-market approach.
Key Takeaways:
(1) Sievert emphasized showing the problem's scale more clearly—specifically, what percentage of HBV patients develop HCC and how many new diagnoses occur annually. She noted that demonstrating a growing problem (HCC incidence increasing at approximately 1.5-1.7% per year in the U.S.) makes the market more attractive to investors. However, she cautioned that limiting our market to only recurrence patients unnecessarily narrows our addressable population.
(2) Sievert urged conducting rigorous financial analysis of the academic toolkit concept. She recommended calculating personnel requirements, manufacturing costs, and determining whether revenue would be recurring or one-time. She noted that fundraising without IP protection is challenging and questioned whether toolkit revenue could realistically generate sufficient capital to support clinical trials. Her key concern was ensuring long-term business sustainability rather than relying on potentially unstable funding sources like NGO partnerships.
Interview Date: August 19th, 2025
Background: Matteus Pan works at Genesis Therapeutics, a biotechnology company leveraging AI and machine learning for drug discovery. His perspective on positioning early-stage biotech platforms and defining clear value propositions provided crucial feedback on LiRA's commercial narrative.
Key Takeaways:
(1) Pan emphasized the need to clearly articulate LiRA's exact value add and reframe our story around what specifically makes the technology innovative. Rather than presenting multiple possible applications, he advised focusing on the core differentiator—whether it's the dual-input specificity, the viral integration marker approach, or the platform's modularity—and building the narrative around that singular strength.
(2) Pan suggested exploring dual revenue streams: positioning LiRA as both a therapeutic development program and as a platform technology that could be licensed to other biopharma companies. This "derisking" strategy, or generating revenue by selling the platform while simultaneously pursuing internal therapeutic development, mirrors successful models in the biotech industry where companies monetize their technology through partnerships while building their own pipeline. Based on Dr. Pan's guidance, we adopted a two-track commercialization strategy that explicitly addresses platform versus therapeutic positioning. Track 1 focuses on the research toolkit as a near-term revenue generator, allowing labs to test multi-input RNA logic without custom development. Track 2 pursues the therapeutic application for HBV-HCC, leveraging our unique viral integration marker approach as the key differentiator.
Interview Date: August 19th, 2025
Background: Karina Padilla is a strategic business operations leader currently working at Genentech in clinical manufacturing and R&D operations. As a Stanford iGEM alum, she provided valuable guidance on presentation structure and commercial strategy.
Key Takeaways:
(1) Padilla emphasized the importance of sequencing our narrative correctly. She advised presenting safety data and the regulatory pathway before discussing go-to-market strategy; audiences need confidence in the product's viability before understanding commercialization plans. She noted that we have strong foundational elements but need to reorder slides to build a more logical, compelling story arc.
(2) Padilla noted that clinical trials are extremely expensive and suggested gathering user data and validation evidence as early as possible before committing to full-scale trials. This de-risking approach helps secure funding and partnerships by demonstrating traction before major capital commitments.
(3) She offered to connect us with contacts at Genentech who have expertise in SOM calculations and market analysis, potentially strengthening our financial projections with industry-standard methodologies.
Market Analysis (TAM/SAM/SOM)
LiRA addresses two distinct markets:
- A therapeutic product for patients with HBV-driven liver cancer.
- A research-use toolkit for labs that want to design and test their own RNA logic systems.
We analyze each separately, using the standard TAM-SAM-SOM framework.
Therapeutic market (HBV-HCC)
Who are the customers? Patients with late-stage hepatocellular carcinoma (HCC) caused by chronic hepatitis B virus (HBV). These patients are the most likely to receive advanced therapies such as immunotherapy or gene therapy.
Total Available Market (TAM): Globally, there are about 400,000 late-stage HBV-HCC patients every year. At an average immunotherapy cost of $100,000 per patient, this is roughly a $40 billion market.
Serviceable Available Market (SAM): HBV accounts for 50-55% of all HCC cases, which narrows the addressable pool to about 200,000 patients per year, or a $20 billion market.
Serviceable Obtainable Market (SOM): For early commercialization, we focus on the U.S.. If we assume LiRA reaches 20% of patients treated at NCI-designated and early-adopting hospitals, this corresponds to about 650 patients per year, or $65 million in obtainable market.
Toolkit Market (Research-Use Only)
Who would use LiRA's toolkit? LiRA is designed for labs that want to test multi-input RNA logic in vitro, or detecting two RNA targets inside the cell and linking them to a reporter or model therapeutic output. This makes it useful for:
- Synthetic biology groups developing circuits.
- Cancer biology labs testing biomarker panels.
- Virology labs studying viral RNA signatures.
- Core facilities offering multi-marker reporter assays.
Convenience matters. Today, most labs are limited to single-biomarker reporters. Even when multi-input systems are attempted, they usually require custom cloning and weeks of troubleshooting. LiRA lowers the barrier: labs can select RNA inputs and immediately run assays with a built-in reporter or model output. This makes proof-of-concept experiments faster, cheaper, and easier, turning multi-marker testing from a specialist task into an off-the-shelf workflow.
Total Available Market (TAM):
- Estimating TAM labs (worldwide):
- Synthetic biology labs: ~13,000 active groups (based on Addgene distribution analysis).
- Industry R&D: ~1,100 labs within 900+ synthetic biology companies.
- Relevant core facilities: ~200 focused on cell-based reporter assays.
- Estimating revenue generated from number of labs: Toolkit pricing is benchmarked against existing RUO (research-use-only) gene circuit kits. If LiRA is priced at $1,000-$3,000 per kit, and each adopting lab buys 1-2 kits per year, the potential spend is in the tens of millions annually.
Total TAM labs ≈ 14,300.
Serviceable Available Market (SAM): The U.S. represents ~25-30% of global synbio/cancer biology capacity. That's ~3,500-4,000 labs who could directly benefit from in vitro RNA logic testing.
Serviceable Obtainable Market (SOM): If we narrow down our scope to the Bay Area, within driving distance of Stanford, UCSF, Berkeley, and associated core facilities are ~200-300 labs. We project adoption by these labs through pilot programs, conferences, and partnerships with core facilities. At an average price of $2,000 per kit, that represents hundreds of thousands in early revenue, which is enough to validate demand, generate case studies, and build credibility for national rollout.
Competitive Landscape
The following analyze the competitive landscape for both of LiRA's products: 1) the therapeutic for HBV-induced HCC, and 2) the research-use only tool for modular RNA programming.
HBV-HCC Therapeutic
Competitive Analysis of LiRA as a HBV-HCC Therapeutic
LiRA differs from existing HBV-HCC therapies in how it identifies cancer cells. While RNAi therapies and therapeutic vaccines target single mechanisms, LiRA requires two signals before activating: viral integration transcripts that mark HBV infection and tumor-specific markers like GPC3. This dual-input design, combined with split-protein safety controls, aims to improve tumor specificity and reduce off-target effects. The system uses liver-targeting lipid nanoparticles for delivery, and because both the input sensors and output proteins can be reprogrammed, the same platform could be adapted to other cancers beyond HBV-HCC.
RUO Tool
Competitive Analysis of LiRA as a RUO Tool for Labs
LiRA is the first off-the-shelf toolkit that lets labs test dual-input RNA logic circuits without custom cloning. Researchers can select two RNA biomarkers, link them through an AND gate, and immediately run assays with built-in reporters or model therapeutic outputs, turning experiments that typically take weeks into work that can be done in days.
Regulatory and Clinical Pathway
Intellectual Property Strategy
Since the start of our project, we understood that LiRA's development exists within a complex intellectual property landscape. Our technology builds directly on RADAR, a programmable RNA-sensing platform invented in the Gao Lab at Stanford. RADAR’s core mechanisms—including its programmable RNA sensor architecture that detects specific cellular transcripts and its system for coupling RNA detection to targeted protein outputs—have been filed as intellectual property by Stanford’s Office of Technology Licensing and subsequently exclusively licensed to RADAR Therapeutics, a company founded by members of the Gao Lab.
Given this foundation, we engaged early with Stanford OTL to map LiRA's patent potential and identify which elements of our work could create defensible intellectual property. Eileen Lee, the Senior Licensing and Strategic Alliances Manager who handled the original RADAR patent filings, reviewed our project in detail over several months. Her assessment provided both validation of LiRA’s novelty and a clear-eyed analysis of the patent challenges we face.
What Makes LiRA Patentable
Eileen helped us identify three areas where LiRA could contribute novel IP beyond the foundational RADAR platform:
1. Conserved HBx transcript sequences
Through bioinformatic analysis of HBV integration patterns across patient datasets, we identified specific regions of the HBx transcript that are consistently retained after viral integration. These sequences have not been previously characterized as biomarker targets and represent potential sequence-specific claims.
2. Viral-plus-cancer biomarker combinations
While individual cancer markers like GPC3 are well established, and RADAR's logic gate architecture is patented, our specific pairing of viral integration markers with endogenous cancer markers represents a novel application. Method claims around this dual-input strategy for HBV-HCC distinguish LiRA from other RNA logic systems and extend RADAR's platform into viral oncology, which is a use case not covered by existing patents.
3. Split-protein therapeutic outputs
Our implementation of split therapeutic proteins (such as split IL-2) as outputs, gated by simultaneous detection of viral and cancer RNAs, offers composition-of-matter and method-of-use claims. This design creates a safety mechanism absent from single-marker therapeutics and provides a clear pathway to demonstrable therapeutic efficacy.
Our Two-Track IP Strategy
We've structured LiRA's IP development to generate near-term value while building toward long-term therapeutic patents.
Track 1: Research Toolkit (Years 1-2)
The research toolkit launches under a Research Use Only (RUO) model, which allows commercialization without requiring the extensive patent protection needed for therapeutics. Our competitive advantage comes from:
- Proprietary marker databases: Our bioinformatic work identifying conserved viral integration sequences and optimal cancer biomarker pairs creates valuable know-how. While key findings will be published for scientific credibility, our full database of validated combinations and design rules remains proprietary.
- Turnkey implementation: We package RADAR's principles into a plug-and-play system with pre-validated constructs, optimized protocols, and technical support. This all falls into operational know-how that would take competitors time to replicate.
- First-mover brand advantage: Early adopters, published case studies, and endorsements from Stanford, UCSF, and Berkeley labs establish LiRA as the standard for multi-input RNA logic experiments.
- Design and utility patents: We will file patents on our specific construct designs, vector architectures, and kit configurations in order to protect our toolkit implementation.
This mirrors successful strategies from companies like Addgene (plasmid distribution) and New England Biolabs (research enzymes), which built substantial businesses through brand, know-how, and selective patent protection rather than broad platform exclusivity.
Track 2: Therapeutic Development (Years 2-8)
For the therapeutic pathway, we are building a robust patent portfolio in parallel with preclinical validation. This work proceeds in three overlapping stages.
Preclinical validation and provisional filings (Years 2-3). As we generate therapeutic efficacy data (e.g. tumor cell killing, immune activation, and survival benefit in animal models), we will file provisional patent applications. These will cover method-of-use claims for treating HBV-HCC by delivering logic-gated therapeutics that activate only when both viral integration markers and cancer biomarkers are present. We will also file composition claims on specific combinations of HBx-targeting sensors, GPC3/AKR1B10 sensors, and split therapeutic proteins like IL-2 or IL-12. If we develop proprietary lipid nanoparticle formulations optimized for liver targeting and circuit delivery, these will be separately patented. Provisional filings establish priority dates and give us twelve months to strengthen claims with additional data before committing to full utility patents.
Securing access to RADAR IP (Years 3-5). In parallel, we will negotiate sublicense arrangements with RADAR Therapeutics and Stanford OTL. Several models are standard in biotech. Under a sublicense agreement, RADAR Therapeutics would grant LiRA rights to use the RADAR platform for HBV-HCC applications in exchange for milestone payments, royalties, or equity. This is a common structure when applications don't compete with the licensee's core focus. Alternatively, a co-development partnership would allow RADAR Therapeutics and LiRA to collaborate on the HBV-HCC indication, sharing development costs and revenues while leveraging RADAR's established expertise. A third path involves strategic acquisition, where RADAR Therapeutics acquires the LiRA program once we demonstrate strong proof of concept. Each approach has successful precedents: Foundation Medicine was acquired by Roche after building on licensed academic IP, Editas Medicine navigated complex CRISPR licensing arrangements across multiple institutions, and Kite Pharma structured partnerships around foundational CAR-T patents.
Expanding patent coverage (Years 5-8). As LiRA advances through preclinical and clinical development, we will continue building our patent estate. Adapting LiRA to other virus-linked cancers like HPV-driven cervical cancer or EBV-associated malignancies generates new method and composition claims for each indication. Ongoing optimization work, such as developing sensors with higher sensitivity or lower background activation, creates additional patents that strengthen our position even as foundational RADAR patents age. Manufacturing and formulation IP, including scalable production methods and stability-enhancing formulations, can be patented independently of the core therapeutic mechanism.
Business Model Canvas and Full Business Plan
LiRA's Business Plan
Go-To-Market Strategy
Our commercialization plan is designed in phases, balancing early revenue with long-term therapeutic development. This phased approach allows us to generate early traction with academic users, validate the technology through published work, and build the credibility and resources needed to advance LiRA as a clinical therapeutic.
Phase 1: Toolkit Launch (Years 1-2)
We will begin by introducing LiRA as a research-use toolkit for synthetic biology and cancer biology labs. Early adoption will focus on the Bay Area, where major academic centers such as Stanford, UCSF, and Berkeley support a critical mass of researchers working with RNA tools. By offering pilot programs to around fifty labs, we can demonstrate LiRA's value in real-world experiments while building case studies and early publications. The appeal is twofold: convenience, with our plug-and-play access to multi-input logic without months of cloning — and speed, enabling proof-of-concept experiments in days. Toolkits will be offered as starter kits priced at roughly $5,000, with additional assay modules and support packages available.
Phase 2: Therapeutic Development (Years 2-8)
In parallel, we will pursue LiRA's therapeutic application for HBV-HCC. This pathway involves collaborations with clinical researchers and NCI-designated hospitals, advancing through preclinical validation and an IND submission with the FDA. Because HBV-HCC is a rare but high-burden indication, LiRA may qualify for Orphan Drug designation, which provides regulatory and market advantages. Our long-term plan is to license or co-develop with pharmaceutical partners once Phase IIa proof of concept is achieved, following the model of other successful RNA therapy startups.
Phase 3: Global Expansion (Year 8+)
After establishing the toolkit in the U.S. and advancing the therapeutic through proof of concept, LiRA will expand outward. The research toolkit will be distributed internationally through partnerships with established reagent companies, while the therapeutic program will progress into broader indications and new geographies where HBV and liver cancer are most prevalent.
Impact and Risks
SWOT Analysis.
LiRA's Long-term Impacts: Positive and Negative
Click any card to view risk mitigation strategies.
Each impact area includes proactive mitigation strategies to ensure responsible development and deployment of LiRA technology.