Presentations- Advancements in Gene Therapy and AAV Vector Technology: Insights from the Penn GTP


The Gene Therapy Program (GTP) at the Perelman School of Medicine at the University of Pennsylvania is making significant contributions to the field of gene therapy. Led by James M. Wilson, MD, PhD, the program focuses on advancing genetic medicines and exploring the potential of adeno-associated virus (AAV) vector technology. The GTP’s innovative research will be showcased at the upcoming American Society of Cell and Gene Therapy (ASGCT) 26th Annual Meeting in Los Angeles, California from May 16 to May 20, 2023.


Exploring AAV Vector Biology:

The GTP team has made remarkable progress in addressing gaps in understanding AAV vector biology, essential for the development of successful gene therapies. At the ASGCT meeting, they will present nine abstracts highlighting their translational science and discovery research. These presentations will shed light on novel applications of genetic medicines for rare and acquired diseases with high unmet needs.


AAV Integrations: Extensive Analysis and Implications:

MD/PhD student Kelly Martins will present the most comprehensive analysis to date of AAV integrations in nonhuman primates (NHPs) and humans. The findings offer insights into the occurrence and implications of AAV integrations following both wild-type infections and vector administration. This oral presentation on May 17 will contribute to our understanding of the safety and efficacy of gene therapies.


Characterizing Vector Genomes:

Research director Jason Lamontagne, PhD, will discuss the deployment of long-read sequencing to characterize the structure of vector genomes in NHPs. This analysis is crucial for assessing the safety and efficacy of gene therapy. Lamontagne’s oral presentation on May 18 will shed light on the implications of these data.


Safety Considerations in AAV Administration:

George Buchlis, PhD, a research director at the GTP, will discuss an important safety concern related to systemic toxicity following high-dose AAV administration. This oral presentation on May 18 will address serotype-dependent hepatocellular damage and complement deposition and activation, enhancing our understanding of potential risks.


Modifying AAV Capsids for Enhanced Safety:

Jacob Hoffman, a PhD candidate, will present a poster outlining the comprehensive analysis of the AAV9 galactose-binding pocket. This work aims to modify AAV capsids, improving safety and de-targeting them from the liver. Such modifications hold the potential to enhance the safety and effectiveness of AAV-based gene therapies.


Novel Applications of Genetic Medicines:

The GTP team will also present research on novel applications of genetic medicines. This includes the use of AAVs to target HER2+ brain metastasis and HER2+ breast-to-brain metastasis. Researchers will share pharmacology and toxicology data, highlighting the use of AAV to express trastuzumab (Herceptin®) in the central nervous system, with the goal of treating patients with HER2+ breast cancer metastases to the brain.


Lipid Nanoparticle (LNP)-mRNA Therapies for Liver Metabolic Diseases:

Vivek Chowdhary, PhD, an associate director of translational research at the GTP, will present data on lipid nanoparticle (LNP)-mRNA therapies for Crigler-Najjar Syndrome Type 1 (CN1), a liver metabolic disease. This research explores an innovative approach beyond conventional AAV gene therapy.


Efficient Gene Insertion through Gene Editing:

Jenny Greig, PhD, a senior director of research at the GTP, will present research on achieving highly efficient site-specific gene insertion using gene editing techniques. The focus will be on Ornithine Transcarbamylase Deficiency (OTCD), highlighting the potential of gene editing for precise and effective treatments.


Overcoming Immune Barriers for AAV Vector Gene Therapy:

The GTP’s research also explores strategies to enable AAV vector gene therapy in the presence of pre-existing humoral immunity. By inhibiting the neonatal Fc receptor, researchers aim to overcome immune barriers and facilitate the effective delivery of AAV-based gene therapies.



The presentations by the Penn GTP at the ASGCT Annual Meeting demonstrate the program’s dedication to advancing gene therapy and AAV vector technology. Through their research, the GTP team aims to address key challenges in the field, including AAV vector biology, safety considerations, and the development of novel applications of genetic medicines. These insights contribute to the understanding and future development of gene therapies for a wide range of diseases. By sharing their findings with the scientific community, the Penn GTP plays a pivotal role in propelling the field of gene therapy forward and bringing us closer to effective treatments for previously untreatable conditions.


In conclusion, the research presented by the Penn GTP highlights the significant progress being made in gene therapy and AAV vector technology. Their investigations into AAV vector biology, safety considerations, and novel applications of genetic medicines provide valuable insights that contribute to the advancement of gene therapies. Through their participation in the ASGCT Annual Meeting, the Penn GTP continues to push the boundaries of scientific knowledge, bringing us closer to transformative treatments for a wide range of diseases.


Reference: Penn GTP