Designing Medicines for One: The Future of Individualized RNA Medicines
Therna Biosciences recently unveiled its collaboration with Charles River to advance individualized medicines for patients with ultra-rare diseases. Our first program is focused on a patient with rapidly progressing form of lung fibrosis caused by a unique mutated gene. With no available treatment options, the need for a tailored RNA medicine was extremely urgent.
Following the announcement, several reporters expressed interest in learning more about Therna’s n=1 strategy, with Ryan Cross at Endpoints News asking how the FDA’s recent draft guidance, which introduces a framework for accelerating tailored, individualized treatments for ultra-rare diseases, could impact the company. This guidance marks an important moment for the field and an opportunity to define how n=1 approaches can be developed with both speed and scientific rigor. In this blog, I outline our vision and approach to advancing n=1 treatments for patients who have no alternative treatment options. Central to this effort is our AI-enabled RNA platform and its alignment with the scientific and regulatory requirements of individualized medicine.
Therna’s approach is built on the premise that RNA can be designed with extreme precision. We have developed an AI-driven platform trained on massive amounts of proprietary experimental data generated in our labs, enabling us to interrogate how RNA behaves in biological systems.
When creating the model, we asked questions about how RNA interacts with its biological environment and how those interactions influence behavior, translation efficiency, tissue and cell type expression and longevity. We also examined RNA structure, stability, and interactions with RNA-binding proteins, as well as how DNA, RNA, and proteins work together within the cell. As a result, our AI model with RNA intelligence can generatively design RNA sequences with characteristics that we want. For example, we can program the mRNA to be expressed exclusively in a tissue or cell type of interest, to be more durable, and achieve high translation efficiency to protein output. Similarly, we can find unique target sites within the transcript and design small oligonucleotides, such as ASOs and siRNAs, to increase, decrease, or fine tune the expression of the mRNA. Rather than producing transient biological signals, these engineered RNA sequences are designed to function as therapeutics.
By integrating computational design with experimental validation, we can generate better RNA medicines faster and translate those designs into candidates suitable for development. This approach has the potential to improve the cost-efficiency of developing highly individualized therapies, enabling programs that would not have been feasible using conventional drug discovery approaches. In doing so, it opens the door to programmable RNA medicines with previously unattainable properties.
While single-patient programs are an important application of our platform, Therna is advancing a broader pipeline of RNA medicines across multiple disease areas with significant unmet need. These efforts leverage the same design and validation framework to develop therapeutics at scale.
Our rationale for advancing individualized medicine is grounded in four core principles:
First, these patients are often overlooked and have no viable treatment options. There is limited commercial incentive for industry to pursue such therapies, and academic institutions typically lack the resources to develop them at scale. We believe there is a responsibility to address this gap and bring forward solutions where none exist.
Second, our AI-enabled platform allows us to rapidly design and validate effective RNA medicines. For these patients, time is of the essence. We have demonstrated the ability to design and experimentally validate candidates in under three months and advance them into pre-clinical development – an unprecedented acceleration of traditional drug development timelines.
Third, each program generates highly valuable data that both validates and strengthens our platform. From initial RNA design through experimental testing and clinical validation, these data improve our models and expand their predictive capabilities. Over time, this learning builds, benefiting not only future n=1 patients but also our broader therapeutic programs.
Fourth, advancing these programs helps establish a viable framework for individualized medicine. While these efforts are less resource-intensive than traditional drug development due to the absence of large clinical trials, they still require meaningful investment. Demonstrating what is possible is an important step toward enabling broader adoption of individualized approaches for patients who need them.
Therna’s approach to individualized medicine reflects a convergence of scientific innovation, regulatory evolution, and urgent patient need. By combining AI-enabled RNA design with rigorous experimental validation, we are establishing a new model for developing therapies for patients who have historically been left behind by traditional drug development. These early programs not only provide a path forward for individuals with ultra-rare diseases, but also generate the data and experience needed to scale this approach more broadly. As the field continues to evolve, we believe Therna will be at the forefront of developing individualized RNA medicines, expanding what is possible for patients and redefining how therapies are developed.