James M. Wilson, MD, PhD
LOS ANGELES — Researchers from the Gene Therapy Program (GTP) at the Perelman School of Medicine at the University of Pennsylvania will present nine abstracts highlighting their translational science and discovery research on gene therapy, gene editing, and adeno-associated virus (AAV) vector technology at the American Society of Cell and Gene Therapy (ASGCT) 26th Annual Meeting on May 16–20, 2023 in Los Angeles, California.
The Penn GTP is an academic program focused on genetic medicines led by James M. Wilson, MD, PhD, the Rose H. Weiss Professor and director at the Orphan Disease Center and a professor of Medicine and Pediatrics at the Perelman School of Medicine.
The team at the Penn GTP has made substantial progress in addressing gaps in the understanding of AAV vector biology relative to the development of successful gene therapies. In addition, they will present novel applications of a broad range of genetic medicines for rare and acquired diseases with high unmet need.
Key Presentations in AAV vector biology
Large-scale Characterization of the Location and Expansion of AAV Integrations in Macaques and Humans Following In Vivo Exposure (Abstract 74)
Kelly Martins, an MD/PhD student, will present the most extensive analysis to date of AAV integrations that occur in nonhuman primates (NHPs) and humans from wild type infections and in NHPs following vector administration. Martins will present the findings in an oral presentation on Wednesday, May 17, 3:45 to 4:00 PM PT in Room 411.
Assessing In Vivo Recombinant AAV DNA by Long-read Sequencing after Gene Therapy (Abstract 179)
Jason Lamontagne, PhD, a research director with the Penn GTP, will outline the deployment of long-read sequencing to characterize the structure of vector genomes in NHPs, and the implications of these data for the safety and efficacy of gene therapy. Lamontagne will present this work in an oral presentation on Thursday, May 18, 3:45 to 4:00 PM PT in Concourse Hall 152 and 153.
High-dose AAV Toxicity in Mice: Serotype-dependent Hepatocellular Damage and Complement Deposition and Activation (Abstract 137)
Another important safety concern relates to systemic toxicity following high-dose AAV administration, which will be discussed in the context of murine models by George Buchlis, PhD, a research director with the Penn GTP. Buchlis will give an oral presentation on Thursday May 18, 1:30 to 1:45 PM PT in Room 411.
Comprehensive Analysis of the AAV9 Galactose-binding Pocket and Its Implications for AAV Vector Biodistribution (Abstract 994)
Jacob Hoffman, a PhD candidate with the Penn GTP, will present ways to modify AAV capsids to de-target them from the liver to improve safety. Hoffman will present a poster on Thursday, May 18, 12:00 to 1:30 PM PT in Exhibit Hall/West Hall A.
Key Presentations in novel applications of genetic medicines
Adeno-associated Virus-mediated Targeting of HER2+ Brain Metastasis (Abstract 144) -and-
Safety Evaluation of Intra-cisterna Magna (ICM) Delivery of a Novel AAV-Trastuzumab Vector to Target HER2+ Breast-to-Brain Metastasis in Rhesus Macaques (Abstract 145)
The use of AAVs to express therapeutic proteins for non-monogenic diseases with unmet need will be presented in two back-to-back presentations. Senior Research Investigator Shweta Aras, PhD, and Marcela Salazar Werner, PhD, a senior director of research, both with the Penn GTP, will describe mouse and NHP pharmacology and toxicology data, respectively, in which AAV is used to express trastuzumab (Herceptin®) in the central nervous system (CNS) with the goal of one day treating patients with HER2+ breast cancer metastases to the brain. Aras and Salazar Werner will present their talks on Thursday, May 18, 1:30 to 1:45 PM and 1:45 to 2:00 PM PT in Room 502 AB.
Pharmacology of Clinical Candidate Lipid Nanoparticle-mediated mRNA-based Therapeutics for Crigler-Najjar Syndrome Type 1 (Abstract 1244)
Moving beyond conventional AAV gene therapy approaches for liver metabolic diseases, Vivek Chowdhary, PhD, an associate director of translational research with the Penn GTP, will present data on the use of lipid nanoparticle (LNP)-mRNA to treat Crigler-Najjar Syndrome Type 1 (CN1). Chowdhary will present a poster on Thursday, May 18, 12:00 to 1:30 PM PT in Exhibit Hall/West Hall A.
Optimal Ratio for Nuclease and Donor AAV Vectors in a Genome Editing Approach for Ornithine Transcarbamylase Deficiency (Abstract 487)
Jenny Greig, PhD, a senior director of research with the Penn GTP, will present on the use of gene editing to achieve highly efficient site-specific gene insertion for Ornithine Transcarbamylase Deficiency (OTCD). Greig will present a poster on Wednesday, May 17, 12:00 to 1:30 PM PT in Exhibit Hall/West Hall A.
A poster presentation entitled Neonatal Fc Receptor Inhibition Enables Adeno-associated Virus Vector Gene Therapy Despite Pre-existing Humoral Immunity (Abstract 723) will be given on Wednesday, 17 May, 12:00 to 1:30 PM PT in Exhibit Hall/West Hall A.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.
The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.