February 12, 2026-UMass Chan Medical School has licensed an investigational adeno-associated virus (AAV) gene therapy program to the Raiden Science Foundation (RSF) to advance clinical development for UBA5 disorder, a rare and life-threatening neurodevelopmental disease. The licensed therapy is based on an AAV9 vector platform designed to deliver a functional copy of the UBA5 gene and restore normal cellular activity in affected patients.
“The Raiden Science Foundation has been instrumental in propelling academic research into UBA5 disorder forward,” said Toloo Taghian, PhD, assistant professor of genetic & cellular medicine and radiology at UMass Chan. “Without their support and backing we couldn’t have reached this important milestone. We look forward to advancing this AAV gene therapy into clinical development.”
UBA5 disorder, also known as developmental and epileptic encephalopathy 44 (DEE44), is caused by biallelic mutations in the UBA5 gene, leading to deficiency of a protein essential for ufmylation, a critical process in cellular homeostasis and neuronal protection. Loss of UBA5 activity results in protein imbalance, neuronal stress, progressive neurodevelopmental impairment, and reduced neuronal function. With fewer than 100 diagnosed cases worldwide and no approved FDA treatments, UBA5 disorder represents a significant unmet medical need. As a single-gene condition, it is particularly well suited for AAV-mediated gene replacement therapy.
The therapeutic candidate utilizes an AAV9 vector, a serotype commonly used in central nervous system gene therapy due to its ability to efficiently transduce neurons and support durable transgene expression. The AAV9-UBA5 construct is engineered to restore UBA5 protein expression in affected tissues, addressing the underlying genetic cause of disease rather than managing symptoms alone. Preclinical studies demonstrated that the AAV9 gene therapy improved disease markers in mouse models, supporting further translational development.
Following these results, UMass Chan submitted a pre-investigational new drug (pre-IND) package to the U.S. Food and Drug Administration in late 2025. With regulatory guidance now in place, the team plans to initiate a Phase I/II first-in-human AAV gene therapy clinical trial at UMass Chan in partnership with RSF.
Miguel Sena-Esteves, PhD, associate professor of genetic & cellular medicine and neurology and director of the Translational Institute for Molecular Therapeutics (TiMT), emphasized the importance of collaborative AAV development models for rare diseases. “By working together with families and foundations like the Raiden Science Foundation, we can build a pipeline that seamlessly moves AAV gene therapy research toward new treatments and clinical trials with regulatory support for patients suffering from rare genetic diseases,” he said.
Established in 2022, TiMT was created to leverage UMass Chan’s experience in AAV and gene therapy development to accelerate early-stage clinical programs for rare disorders. The institute provides infrastructure for AAV vector manufacturing support, regulatory strategy, drug-enabling studies, and first-in-human trial readiness. By integrating AAV development expertise with clinical translation capabilities, TiMT aims to reduce costs and expand access to innovative gene therapies.
The Raiden Science Foundation was founded by Tommy and Linda Pham after their son Raiden was diagnosed with UBA5 disorder in 2021. In 2022, RSF initiated funding for the AAV9 gene therapy research at UMass Chan, enabling development of the UBA5-targeted AAV vector and supporting preclinical validation.
“UBA5 disorder steals development, movement and childhood,” said Tommy Pham, co-founder and president of RSF. “It is a single-gene disorder with no approved FDA treatments or cures, making it well suited for AAV gene therapy interventions.”
The licensing agreement establishes a collaborative framework to advance the AAV9 gene therapy program through clinical development, with shared focus on regulatory milestones, intellectual property, funding strategy, and accelerated translation. For patient-led nonprofit organizations like RSF, the objective is clear: transform academic AAV innovation into viable clinical treatment options for families affected by rare genetic disease.
