Researchers from Mass General Brigham and the Mass General Brigham Gene and Cell Therapy Institute – a hub of innovation dedicated to accelerating groundbreaking research, conducting clinical trials and developing FDA-approved treatments in gene and cell therapy – will present new data at the 2025 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, taking place May 13-17 in New Orleans.
The ASGCT Annual Meeting is the premier event dedicated to gene and cell therapy research, innovation, clinical trials and research discoveries. Presentations from Mass General Brigham investigators include developments and work with rare and ultrarare diseases, brain cancer, and neurodegenerative diseases, as well as new strategies to improve care delivery and accelerate translation from lab to clinic.
“We pride ourselves on being at the cutting edge of gene and cell therapies, while focusing on improving outcomes for patients. That is why we are particularly excited to share recent research and have discussions with the broader community at ASGCT,” said Nathan L. Yozwiak, PhD, Head of Research at the Mass General Brigham Gene and Cell Therapy Institute. “Leaders at our institute will present impactful findings from preclinical research that have the potential to address some of the toughest challenges in genetic disease – bringing us one step closer to safer, more effective therapies for patients.”
The Mass General Brigham Gene and Cell Therapy Institute was established in 2022 to fuel the discovery and development of targeted, transformative treatments that have the potential to cure diseases or halt their progression. The institute unites more than 500 researchers and clinicians dedicated to advancing gene and cell therapy for first-in-human clinical trials, and ultimately, life-saving treatments for patients.
Below are a few highlights from Mass General Brigham presenters at this year’s conference (all times are CT). View all abstracts here.
Optimizing Focused Ultrasound Parameters for Enhanced AAV Delivery Across the Blood-Brain Barrier for the Treatment of Neurodegenerative Diseases (abstract 48)
Bernie Owusu-Yaw, PhD, Brigham and Women’s Hospital
Tuesday, May 13, 1:30-3:15 pm, room 288-290
Delivering gene therapy to the brain remains a major hurdle in treating neurodegenerative diseases due to the restrictive nature of the blood-brain barrier (BBB). While adeno-associated virus (AAV) vectors have shown promise, their ability to cross the BBB remains limited. To address this, researchers are exploring focused ultrasound (FUS) combined with microbubbles as a non-invasive strategy to transiently open the BBB and enable targeted delivery of AAVs. Across a range of tested pressures and doses, FUS-mediated BBB opening led to significantly higher neuronal transduction in the treated hemisphere with no observed tissue damage, even under more aggressive sonication conditions. There was no direct correlation between the volume of BBB opening and transduction efficiency, highlighting the need for further investigation into the underlying mechanisms. These findings underscore the potential of FUS as a safe and tunable method to improve gene therapy delivery to the brain.
A Human Cell-Based Platform for Testing Olfactory Ensheathing Cells as Vectors for Cancer Gene Therapy in hiPSC-derived Brain-Glioma Assembloids (abstract 487)
Elie Roumieh, MD, Massachusetts General Hospital
Wednesday, May 14, 12:15-1:00 pm, Exhibit Theater
Olfactory ensheathing cells (OECs) are a hybrid glial population known to migrate through the brain and accumulate at sites of tumorigenesis, suggesting their potential as vehicles for delivering therapeutic transgenes to central nervous system (CNS) tumors. Researchers aimed to further characterize the properties of mucosal OECs, which could be harvested from patients and engineered for personalized cell-based therapies. In a mouse model bearing brain-implanted gliomas, the team demonstrated that mucosal OECs labeled with MPZ-Cre clustered significantly around tumor sites. Building on this, the team established a human cell culture platform by isolating OECs from nasal biopsies and validated their identity using canonical markers such as p75NGFR and MPZ. These OECs showed robust expansion, successful cryopreservation, and efficient lentiviral transduction. To model tumor interactions, researchers co-cultured human cerebral organoids with glioma cells, generating assembloids that revealed significant glioma invasion. This new brain-glioma assembloid platform provides a valuable system for studying OEC migration and evaluating the therapeutic potential of OEC-delivered factors against tumor growth, with functional studies ongoing.
Investigating Blood-Brain Barrier Functionality in ACTA2 Multisystemic Smooth Muscle Dysfunction Syndrome: A Murine Model Study (abstract 132)
Aarushi Gandhi, PhD, Massachusetts General Hospital
Wednesday, May 14, 3:45-5:30 pm, New Orleans Theater C, New Orleans Theater C
Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS) is an ultrarare monogenic disorder caused by a missense mutation in the ACTA2 gene, leading to shear stress on large vessels, microvascular dysfunction, and blood-brain barrier (BBB) abnormalities. Researchers developed a conditional knock-in ACTA2 R179H mouse model to characterize how this vasculopathy affects the BBB and to explore whether CRISPR base editing could restore BBB integrity and prevent neurodegeneration. Using in vitro BBB models, two-photon microscopy, and histological analysis, the team observed significant BBB dysfunction, leakage, and accelerated neurodegeneration resembling neuronal proteinopathies. Delivery of CRISPR-Cas9 adenine base editing via adeno-associated virus constructs corrected the ACTA2 mutation, successfully restoring smooth muscle contractility and reducing BBB permeability. Histological findings showed that targeted correction improved myelination and reduced pathological microglial and astrocytic activation. Future research will focus on optimizing AAV delivery methods to enhance therapeutic outcomes.
As New Gene and Cell Therapies Emerge from Academia, We Must RISE to the Opportunity (poster 1341)
Nandhitha Uma Naresh, PhD, Mass General Brigham Gene and Cell Therapy Institute
Wednesday, May 14, 5:30–7:00 pm, Poster Hall 12
With over 30 FDA-approved products, the cell and gene therapy (CGT) sector has rapidly expanded, fueled by a surge in clinical trials and early-stage research. Academic medical centers (AMCs) play a critical role in this progress, but advancing new CGTs to the clinic remains a lengthy and costly process. Researchers propose a framework called RISE to help AMCs better support CGT innovation. The model emphasizes Resource sharing, Interdisciplinary collaboration, Sustainable funding, and Educational outreach to bridge translational gaps. By establishing comprehensive institutional support beyond financial investment alone, the RISE model aims to help promising therapies avoid the "valley of death" and reach patients more efficiently. Without such focused infrastructure, many academic CGT innovations risk stalling before they can realize their potential.
Nick Todd, PhD, Brigham and Women’s Hospital and Mass General Brigham Gene and Cell Therapy Institute
Wednesday, May 14, 5:30-7:00 pm, Poster Hall 12
Crossing the blood-brain barrier (BBB) remains a major challenge for gene therapies targeting neurological diseases. To address this, researchers are combining focused ultrasound (FUS) technology with a novel AAV capsid, AAV.CPP16, designed for enhanced BBB penetrance. AAV.CPP16 incorporates a cell-penetrating peptide into the AAV9 capsid and has previously shown >70% neuronal transduction in FUS-targeted regions in mice at a fraction of the clinical AAV9 dose. In this study, the team evaluated the clinical translatability of the FUS + AAV.CPP16 approach using a human clinical FUS system in two rats and one non-human primate (NHP). FUS was guided by MRI and paired with real-time feedback control to steer sonications across up to 32 targets per session. Post-treatment imaging confirmed successful BBB opening in targeted deep brain regions with no signs of hemorrhage. Strong neuronal transduction was observed even at low systemic AAV doses, particularly in FUS-targeted areas. These results support the feasibility of advancing this combined gene delivery strategy into larger preclinical models and, eventually, clinical testing.
Gene Replacement Therapy for Pulmonary Lymphangioleiomyomatosis (abstract 449)
Yan Tang, PhD, Brigham and Women’s Hospital
Saturday, May 17, 10:15-12:00 pm, Room 293 – 296
Pulmonary lymphangioleiomyomatosis (LAM) is a rare genetic lung disease that is characterized by aberrant mTORC1 hyperactivity caused by inactivating mutations of the tumor suppressor genes tuberous sclerosis complex 1 or 2 (Tsc1 or Tsc2) genes. Rapamycin (sirolimus), an mTORC1 inhibitor, is FDA-approved for the treatment of LAM, although ongoing loss of lung function and need for lung transplantation can still occur. Thus, there is an urgent need to develop new therapies for the treatment of LAM. Given that LAM is caused by mutations in a single gene, either TSC1 or TSC2 (more common), gene replacement therapy presents a potential therapeutic strategy by introducing functional TSC1 or TSC2 genes into affected cells. In this study, Researchers demonstrate the efficacy of LNP-based mRNA therapy in a preclinical model of LAM. The team’s lung-targeting LNPs efficiently delivered mouse Tsc2 mRNA to restore TSC2 tumor suppressor function in tumor nodules, resulting in a significant reduction in tumor burden. This research establishes mRNA-loaded LNPs as a promising therapeutic platform for the treatment of LAM.
About Mass General Brigham
Mass General Brigham is an integrated academic healthcare system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.