Seong-Wook Lee, CEO and founder of Rznomics, has spent more than two decades advancing trans-splicing ribozyme (TSR) technology as a novel RNA editing platform. After nearly 20 years in academia, he founded Rznomics to translate the approach into therapies for genetic and intractable diseases. With FDA-cleared clinical programmes, strategic partnerships, and a growing circular RNA platform, Lee aims to establish TSR as a globally recognised therapeutic modality and position Rznomics at the forefront of next-generation RNA medicine.
You spent nearly 20 years in academia before founding Rznomics, focusing throughout on trans-splicing ribozyme research. What was the scientific conviction that drove that commitment?
My interest in RNA mechanisms began during my doctoral studies at Cornell University, where I was researching viral replication mechanisms and first encountered the therapeutic potential of RNA biology. I then moved to Duke University Medical Center for my postdoctoral work, joining the laboratory of Professor Sullenger, who was the first researcher in the world to announce trans-splicing ribozymes and who continues to serve as a scientific advisor to Rznomics today. At the time, gene therapy was widely regarded as the most promising approach to fundamentally treating genetic disease, but most of the work being done focused on expressing the wild-type gene in the patient – essentially replacing a faulty instruction with a correct one. What our approach was trying to do was something more fundamental: to repair or replace the mutant gene itself, at the RNA level, not at the DNA level. The trans-splicing ribozyme approach targets the mutant RNA directly and replaces the downstream region with the correct sequence, restoring normal protein function. That is a more precise and more natural form of correction than simply adding a new gene on top of a faulty one.
At the time, gene editing approaches were only just beginning to emerge in very primitive form – zinc finger proteins were appearing in the literature, and the broader concept of editing rather than simply supplementing was starting to take shape. But I was convinced that targeting the RNA directly was the right direction. I returned to Korea in 1997 as a professor at Dankook University, and spent nearly 20 years there engineering and optimising the ribozyme before founding Rznomics in 2017. I stayed in academic research because that environment gave me the freedom to concentrate on optimisation without external pressure to move faster than the science permitted. I was fortunate also to receive significant government funding, particularly around 2012, which allowed me to pursue the deep optimisation work that this technology genuinely required.
Is the RNA approach also inherently safer than DNA editing?
That was always one of the central arguments in its favour. Because TSR targets RNA rather than DNA, we do not touch the genome itself. The concerns that surrounded gene therapy in the 1990s and 2000s – and there were many, because the viral delivery systems of that era were immature and safety issues were real – were largely connected to permanent changes at the DNA level. The TSR approach sidesteps those concerns. The transient nature of RNA also means that the expression is regulated by the endogenous target RNA itself: the ribozyme could only act when and where the target RNA is expressed, at naturally occurring levels. That precision in regulation is a core advantage, particularly for diseases where the therapeutic window is narrow – where too much or too little expression of the corrected gene creates its own problems.
The limitation of the RNA approach, of course, is that its effects are transient by definition. To address that, we have been using AAV viral vectors to allow permanent expression of the TSR construct mainly in nondividing cells, which gives us a durable one-shot treatment. We are also now developing a DNA-based approach to express TSR without touching the genome directly. And in parallel, for indications where systemic injection and repeat dosing are important, we are beginning to develop an RNA therapeutic form of TSR – which we believe can expand the addressable indication set considerably.
Looking at your pipeline, your lead programme RZ-001 is the most advanced. You recently received IND approvals from both the US FDA and the Korean MFDS, which you have described as a major milestone. What does that mean for the company?
It carries two distinct and very significant meanings for us. The first is simply the evidence that TSR works in human beings. Rznomics is the only company in the world currently using trans-splicing ribozyme technology as a therapeutic modality. Nobody else has human data on this approach. Demonstrating that TSR is active in the clinic – that it functions as intended in actual patients – is a validation that the entire field, and our investors, have been waiting for.
The second meaning is safety. One of the most important questions surrounding a novel RNA modality is whether it causes off-target effects or unexpected cellular disturbances. In our RZ-001 programme, we have so far seen no such issues. The TSR platform is proving to be safe in the clinic, and that is enormously encouraging – not just for RZ-001, but for the credibility of the entire platform. Beyond the IND approvals, RZ-001 has also orphan drug designation (ODD) and fast track designation for both HCC and GBM and furthermore received Regenerative Medicine Advanced Therapy (RMAT) designation for HCC from the US FDA, and the WHO has assigned it the International Nonproprietary Name “Taspitimagene advec” – a formal step that places it within the international pharmacological nomenclature and marks the first stage of global commercialisation for the TSR modality. Our mission has always been to offer life-changing alternatives to patients with intractable diseases for whom no treatments currently exist, and these designations confirm that the regulatory community recognises what we are trying to do.
After we presented our early clinical data for HCC at the AACR Annual meeting in April 2026 in an oral presentation, the level of interest from global pharmaceutical companies increased significantly and rapidly. Within approximately three weeks we were in discussions with major companies. We are continuing to advance the ongoing clinical work while exploring what form those collaborations might take at the appropriate stage of development.
Can you walk us through the clinical status of RZ-001 specifically, and the GBM programme?
RZ-001 is being developed across two oncology indications. The target is hTERT, which is overexpressed across a broad range of tumour types, which means the platform has real potential to expand beyond the initial indications. We are currently advancing studies in hepatocellular carcinoma and glioblastoma multiforme.
In the GBM programme, we are in phase I. We have five cohorts planned and have completed the fourth. The study targets patients with resectable localised multiple recurrence and the treatment is delivered by directly intracerebral injection of RZ-001 to the margins of the resection cavity after surgical resection is complete. We are monitoring safety and tolerability as our primary endpoint and MTD determination and RP2D selection will be performed. Efficacy including duration of response (DOR) will be a secondary endpoint. We presented early safety and interim efficacy data at ESMO Asia conference in Singapore last December and ASNO conference in June 2026, and the results have been encouraging. We are now continuously monitoring the enrolled patients after injection.
For the oncology programme we chose an adenoviral vector deliberately. In an oncology setting, we do not want the therapeutic DNA to remain permanently in the cell. The adenoviral vector gives us a transient approach – what I sometimes describe as a hit-and-run mechanism – which is appropriate for oncology because you want the treatment to act and then clear. We are now also beginning to develop an RNA-based version of the TSR therapeutic for oncology, to enable systemic injection and the possibility of repeat dosing.
How do you select indications and manage pipeline expansion without spreading the company too thin?
We have a structured framework for thinking about which indications are genuinely well matched to our approach. TSR has specific competitive advantages in certain disease categories. The first is diseases that require precise regulation of transgene expression. Because our ribozyme could act only when and where the target RNA is expressed at endogenous levels, we can achieve a degree of regulatory precision that classical gene therapy, which simply expresses a transgene at whatever level the vector permits, cannot easily replicate. For diseases where too much or too little expression of a corrected gene causes harm, that precision is critical.
The second category is haploinsufficient diseases – particularly autosomal dominant conditions where inhibiting the mutant gene alone is not sufficient, and where you also need to restore wild-type expression above a certain threshold. TSR can both inhibit the mutant transcript and express the corrected sequence, which many other approaches cannot do in a single intervention.
The third category is diseases caused by many different mutations in the same gene. Because TSR replaces the entire downstream region of the target RNA from a defined splice point, a single TSR construct can be effective across a wide range of mutations – rather than requiring a different therapeutic for each mutation variant.
Using this framework, we have mapped approximately 200 indications that are accessible to our approach. We cannot pursue all of them ourselves, and we do not intend to. Our strategy is to advance the most clinically compelling programmes either in-house or through partnerships and collaborations with other companies.
You have also been developing a circular RNA platform. How does it relate to the TSR work, and what differentiates your approach?
The circular RNA platform is our next major technology development. We generate circular RNA using the same ribozyme mechanism that underlies TSR, but the application is different. Most companies working in circular RNA today use what is known as the PIE pathway – the permuted intron-exon method. The PIE method is effective but introduces extraneous sequences into the gene of interest as a consequence of the splicing mechanism it uses. These extra sequences are not part of the intended payload, and while some researchers consider them acceptable, others have raised concerns that they may trigger immune responses.
Our approach generates circular RNA that contains only the gene of interest – no extraneous sequences. That means no uncertainty about whether additional sequences are causing unintended biological effects. This Self-Circularized RNA platform is specifically designed to overcome the short half-life of linear RNA in vivo. By maximising in vivo stability and dramatically extending administration intervals, we expect it to enhance therapeutic efficiency in ways that existing linear mRNA technologies cannot achieve – addressing unmet needs that conventional mRNA approaches have difficulty resolving. We believe this is a meaningful differentiation. That said, the circular RNA platform is at an earlier stage of development than our TSR clinical work, and our primary focus remains on advancing TSR through the clinic. For the circular RNA programme in particular, we are looking to build partnerships with best-in-class delivery companies, particularly in Korea, where there are several strong players.
China is dominating the in vivo CAR-T deal landscape – approximately 7.5 billion USD in deals in that space alone last year. How do you think about regional competition and Korea’s position?
China’s achievements in this space are genuinely remarkable. The deal volumes, the clinical stage programmes, the pace of execution – it is impressive and worth acknowledging directly. In vivo CAR-T in particular has shown early clinical success in blood cancers, and the patient experience advantages will be significant: no lymphodepletion required, no need for highly specialised hospital facilities. I attended ASGCT last month and was struck by just how many sessions – more than 50 oral presentations – were dedicated to themes related to in vivo CAR-T approaches. The momentum in this field is substantial.
In terms of where Korea sits, I think Korea has genuine competitive strength in delivery technology. We work with several strong Korean delivery companies, and I believe Korean companies are somewhat behind China in clinical-stage CAR-T development today, but that gap will close quickly. In terms of my own company, we are not in direct competition with the major Chinese in vivo CAR-T developers, because our modality is fundamentally different. Where collaboration is relevant – particularly on delivery – that is how we approach it.
What is your partnership strategy, both for TSR and for the broader platform?
The Eli Lilly partnership has been an important reference point for us, and we are now actively expanding our global business development activity. The framework we operate across has three distinct channels. The first is pipeline deals – partnerships around specific programmes such as our Alzheimer’s disease pipeline, RZ-003. The second is platform deals – licensing our TSR or circular RNA technology to companies that want to build their own programmes on top of our foundational science. The third is IP licensing – our fundamental patents, including our own circular RNA platform technology, can be licensed for research or commercial applications. We have companies currently in materials transfer agreements evaluating our technology across more than one of these channels, though I cannot name them at this stage.
In terms of how we structure those partnerships, we take a two-track approach. For early-stage platforms, we use co-development and option-based models with global big pharma, which is how our Eli Lilly collaboration is structured. For clinically advanced assets backed by human data, we pursue regional licensing-out and global co-development agreements to maximise commercial velocity and value. Geographically, we are prioritising the United States, Europe, and the APAC region, with our operational focus weighted heavily toward US-centred global trials following the RMAT designation for RZ-001.
The longer-term vision is clear: we want to develop our own biopharmaceutical products and bring them to patients ourselves. But at our current stage –early clinical data, a novel modality that requires ongoing proof of concept – the priority is accumulating experience, building credibility through real clinical results, and achieving the financial stability that allows us to execute that long-term vision on our own terms.
Manufacturing is often cited as one of the key bottlenecks in RNA and gene therapy. How are you approaching it?
For our viral vector programmes, we are working with established contract manufacturing partners – Charles River for the adenoviral vector we use in oncology and Fujifilm for the AAV vector for RZ-004 to treat the genetic rare retinal disease retinitis pigmentosa. For RNA manufacturing, we are at an earlier stage. We have not yet reached the manufacturing phase for our RNA therapeutic programmes, and we are in early-stage development work at the laboratory level rather than at process scale. As those programmes advance, we will engage with external RNA manufacturing partners in the same way we have approached viral vector production. We are realistic about what a company of our size can and should do in-house.
Fundraising for a novel modality, and then taking the company public during one of the most difficult periods for biotech financing globally – how did you navigate that?
The early period was genuinely difficult. Investors were interested in the science, but the response was consistent: your technology is fascinating, but nobody has proven it works in humans yet. We are not sure we can invest in something this new. Despite that, some investors did share our conviction, and we were able to build the company step by step.
The approach I took was to treat every meaningful milestone as a trust-building event with our investor community. Orphan drug designation (ODD), the fast track designation from the US FDA, IND approvals from Korea and the United States – each of these gave investors something concrete to assess, a reason to believe that the regulatory authorities were taking our work seriously. That accumulated track record was what made each subsequent fundraising round more achievable.
The pre-IPO round in 2024 was the hardest. The post-COVID global funding environment had deteriorated significantly, and we had to accept a valuation reduction. One of the conditions attached to the listing was achieving a global licensing deal – a requirement that, if not met, would trigger a further 20 percent reduction in our valuation. We accepted those terms because we had early promising clinical results at the time and were confident we could achieve the milestone. The Eli Lilly partnership was one of the principal reasons we were ultimately able to list on KOSDAQ.
Looking five years ahead, to 2031, what are your priorities?
The immediate priority is clinical data. Every conversation we have with investors, partners, and the scientific community eventually comes to the same point: show us the patient data. That is the only thing that will fully validate the platform in the eyes of the world, and it is what we are focused on delivering.
Beyond that, I want to see TSR established as a recognised standard therapeutic approach for a meaningful set of diseases – initially the genetic and degenerative indications we are targeting now, but expanding to other disease categories over time. The platform has an extraordinary range of potential applications; we have identified approximately 200 targetable indications, and while we cannot pursue all of them ourselves, I hope that in five years we are advancing our own programmes in several of these while partners are advancing others.
The next platform after TSR is circular RNA, and we are already working on a further platform beyond that, which I cannot describe in detail yet. The underlying reality is that many diseases remain completely beyond the reach of current therapeutic modalities – rare genetic diseases in particular. If our TSR approach can address even a fraction of that unmet need, and if the platforms that follow it can address more, that is the scientific mission this company was founded to pursue. The ambition we have set for ourselves is to become a next-generation RNA editing platform company that leads global standards – not simply a biotech that develops individual products, but an organisation that defines what RNA editing can achieve across human disease.
You are a scientist who became a chief executive. What is your philosophy on balancing those two roles?
It is genuinely difficult to find business partners who share the same philosophy as a scientist-founder, especially when your company is working in a modality that most of the industry does not yet fully understand. In the early years, I was involved in both the science and the business development myself, which was extremely demanding. What has changed, fortunately, is that I now have board members and senior colleagues at the C-level who bring deep business development and financial expertise and who are genuinely aligned with our mission. That has allowed me to divide my time roughly equally – approximately 50 percent on the science and research, 50 percent on the business. For a company like ours, where the science is the foundation of everything, I believe that balance is about right.
