Dr Shannon E Boye, Co-Founder and Chief Scientific Officer of Atsena Therapeutics, writes about the company’s journey to the clinic for a challenging ocular gene therapy target.  

I have worked for nearly 20 years across academia and the biopharmaceutical industry to develop gene therapies for inherited retinal diseases. I met Sanford Boye, my other half in life and in science, in the lab. If you name any inherited retinal disease, the likelihood is that we have worked on it. We have experienced the thrill of laboratory breakthroughs that could change the lives of patients and the disappointment when those technologies were out-licensed to companies that did not realise their full potential. We finally decided to co-found Atsena Therapeutics so that the scientific advancements from our lab at the University of Florida would reach the patients who needed them most. Atsena now has a robust pipeline of gene therapies, including our lead candidate ATSN-201, a potential best-in-class treatment for X-linked retinoschisis (XLRS), but my journey began with an unlikely undergraduate major: marine biology.  

As a student at Farleigh Dickinson University, I was lucky enough to work one summer at the Whitney Laboratory for Marine Science, where I learned that while it might be difficult to make a living swimming with dolphins, there were many opportunities to contribute to exciting biomedical research. Following my graduation, I entered the neuroscience Ph.D. programme at the University of Florida. This university has been home to some of the greatest discoveries and developments in the history of gene therapy research, which is why I focused my thesis on gene therapies for inherited retinal diseases, particularly GUCY2D-associated Leber congenital amaurosis (LCA1). This condition is typically diagnosed within the first few months of life and causes profound vision impairment if not total blindness. The lab studied the biochemical underpinnings of this disease using chicken models, investigating whether we could use gene therapy to restore vision in chickens with LCA1. Each morning I would collect eggs, and we would make small holes to inject the embryos with healthy gene product. So much had to go right for a treated embryo to make it all the way to hatch – injecting at exactly the right site, making sure the incubator temperature and humidity were perfect – but eventually little chicks emerged from these eggs. Chickens are very visually guided creatures, so it was obvious as the newly hatched chicks walked around our lab bench pecking at jewelry and M&Ms we had laid out that our gene replacement had been successful: they could see. 

Closing the gap between preclinical and clinical research

Exciting as it was to find success in the chicken models, I have never been the kind of researcher who is content to conduct experiments for their own sake. After graduate school, I stayed in Gainesville for my postdoctoral research, eventually rising to become a Professor and Chief of the Division of Cellular and Molecular Therapy in the university’s Department of Pediatrics, always remaining motivated by the opportunity to transform the lives of patients.  As I progressed in my academic career, I followed a path that is familiar to any researcher. My lab would discover new gene therapy technologies that we would advance through proof-of-concept preclinical studies, and after securing the intellectual property rights, we would out-license these technologies to companies ranging from large pharmaceutical organisations to small biotechnology start-ups. Our thinking was that these companies had the resources and infrastructure needed to bring these technologies into the clinic. However, no matter the company, the outcome was the same: our technologies – such as the LCA1 gene therapy I first studied in graduate school – were not reaching the patients for whom they were intended.  

As this disappointing cycle repeated itself over the years, my frustration mounted. I knew there had to be a way to translate our lab’s discoveries into clinically meaningful therapies. The gap between preclinical and clinical research is often referred to as the “valley of death.” It’s an appropriately intimidating name for the wide distance between the sort of preclinical studies that academics conduct and the capital-intensive clinical studies that biopharmaceutical companies traditionally undertake. For gene therapies in particular, this valley is deep. It costs millions of dollars to develop the adeno-associated virus (AAV) vectors that deliver gene therapy cargo at the stringency and scale required for clinical studies, not to mention any of the other significant costs associated with these studies. These are costs that academics simply cannot afford. It seemed there was only one solution to this problem: we needed to start a company that could take our gene therapy technologies through the clinic to the patients who needed them most. 

Prioritising sound science

Atsena Therapeutics was founded on the belief that making the best decisions for patients would ultimately bring us the best results both medically and ultimately commercially. As an academic, I was part of many conversations with companies that did not choose to prioritise sound science, and they ultimately paid the price by sacrificing clinical differentiation for the sake of cost and convenience. For instance, different AAVs have different properties that determine their efficacy for treating certain diseases. If you are looking to develop truly impactful gene therapies across indications, you cannot take a one-size-fits-all approach to AAVs. However, some companies decide that because it is easier to manufacture one sort of AAV than another, they will use that one AAV across all indications. This approach may appear to offer some short-term efficiencies, but really it undermines clinical differentiation and reduces the potential patient benefit.  

At Atsena, we take a different approach. We utilise AAV technologies that are specially engineered to overcome the limitations of current gene therapies and are uniquely suited for the prevention or reversal of blindness caused by inherited retinal diseases.  

Shortly after forming Atsena, we were able to in-license the LCA1 therapy that I had been developing since graduate school and named the therapy ATSN-101. Atsena continues to develop ATSN-101, a first-in-class gene therapy for the treatment of LCA1, and has gained Rare Pediatric Disease Designation, Regenerative Medicine Advanced Therapy Designation and Orphan Drug Designation from the US Food and Drug Administration (FDA), underscoring the significant unmet needs of these patients. In a Phase I/II study, ATSN-101 demonstrated an up to 10,000-fold improvement in vision. One of the treated patients saw snowflakes for the first time – this story still brings tears to my eyes.  These results validated the clinical importance of our technology, and we were proud to announce an exclusive license agreement with Nippon Shinyaku for the commercialisation of ATSN-101 in the US, along with its development and commercialisation in Japan. We are pleased that this programme, which we spent so many years working on, is now close to reaching the patients who need it most. 

Creating a novel vector

Our lead programme, ATSN-201 for the treatment of XLRS, is also an excellent example of why it is vital to adjust the choice of AAV based on target indication. XLRS is a rare inherited retinal disease caused by mutations in the RS1 gene. The condition is characterised by schisis, or abnormal splitting of retinal layers, which causes impaired visual acuity that is not correctable with glasses and leads to progressive vision loss and ultimately blindness. Throughout the course of the disease, patients are at risk of retinal tears and detachments, and loss of vision limits them from engaging in various activities in their work and home lives. XLRS primarily affects men and is typically diagnosed in early childhood. Approximately 30,000 men in the US and Europe have XLRS, for which there are currently no approved treatments. ATSN-201 works to deliver a healthy copy of the RS1 gene and restore vision to patients, but this would not be possible without AAV.SPR, our novel spreading capsid.  

Development of AAV.SPR stemmed from the need to achieve therapeutic levels of gene expression in photoreceptors of the central retina while avoiding the surgical risks of foveal detachment. When using a subretinal approach, traditional AAV vectors need to be delivered precisely to the region of the retina that is most affected. For XLRS, this would involve detaching the fovea, which is potentially very risky. It has been shown in other clinical trials that some patients exhibit a loss of central retinal thickness and even a loss of visual acuity if they have their fovea detached. For this reason, other companies have pursued an intravitreal approach to treating XLRS. However, intravitreally injected AAV vectors, whether naturally occurring or engineered, do not efficiently reach photoreceptors of patients, and they can also lead to inflammation because the vitreous is not an immune-privileged space. This puts patients at risk without any prospect of benefit. Our solution? AAV.SPR, a vector that maintains the efficiency of photoreceptor gene delivery afforded by subretinally injected vectors but avoids the need for foveal detachment. AAV.SPR can be placed in the peripheral subretinal space, and by virtue of its spreading behavior, it can move past the margins of the original subretinal injection bleb and deliver the healthy gene product to the foveal cones without the need to surgically detach the sensitive retinal region. AAV.SPR also spreads to cover a larger area of the retina than benchmark AAVs, resulting in greater efficacy.  

In our ongoing Phase I/II/III LIGHTHOUSE Trial, we have shown that ATSN-201 is the first therapy capable of reversing structural damage in the retina. It doesn’t just halt the progression of XLRS, but it also leads to structural and functional improvements within weeks of treatment. ATSN-201 leads to closure of schisis cavities both inside and outside the bleb area, durable improvements in retinal thickness, and clinically meaningful improvements in retinal sensitivity. Patients have reported seeing a star for the first time and noticing that vision in their treated eye feels like an ‘HD TV.’ Importantly, the subretinal injections have been well tolerated at all dose levels, and the therapy demonstrated an excellent safety profile in the low and intermediate dose levels. 

Now, our team is focused on dosing the paediatric cohort of the LIGHTHOUSE Trial and advancing the study to the pivotal cohort, which is expected to begin enrolling in the first quarter of 2026. We hope to file a Biologics License Application (BLA) with the FDA in early 2028; this has the potential to be an incredible milestone for a company founded by frustrated academics who took a leap into the unknown world of industry to realise the therapeutic potential of their discoveries. While we are very excited by the progress of ATSN-201 and the rest of our pipeline, we believe AAV.SPR and our other AAV delivery technologies can benefit patients with a range of inherited retinal diseases. After all, reaching as many patients as possible is the reason we founded Atsena in the first place.  

About the author

Dr Shannon E Boye is Co-Founder and Chief Scientific Officer of Atsena Therapeutics, and Professor and Associate Chief of Cellular and Molecular Therapy at the University of Florida. A pioneer in gene therapy for inherited retinal diseases, she has authored 50+ papers and received major awards from ARVO, Pfizer, and the Foundation Fighting Blindness. 

From DDW Volume 27 – Issue 1, Winter 2025/2026 – Read the digital issue here