Bioengineering Seminar
"Directed Evolution of New AAV Vectors for Clinical Gene Therapy" - David V. Schaffer - University of California, Berkeley
Co-hosted by Georgia Tech's Institute for Bioengineering and Bioscience and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
David V. Schaffer
Professor
Director of QB3
Director of Bakar BioEnginuity Hub
Department of Chemical & Biomolecular Engineering
University of California, Berkeley
**Register HERE to attend virtually
ABSTRACT
Gene therapy has experienced an increasing number of successful human clinical trials, leading to 7 FDA approved products using delivery vectors based on adeno-associated viruses (AAV). These successes were possible due to the identification of specific disease targets for which natural variants of AAV have sufficient delivery efficiency. However, vectors face a number of barriers and shortcomings that preclude their extension to most human diseases, including limited delivery to target cells, pre-existing antibodies against AAVs, suboptimal biodistribution, limited spread within tissues, and/or an inability to target delivery to specific cells. These barriers are not surprising, since the parent viruses upon which vectors are based were not evolved by nature for our convenience to use as human therapeutics. Unfortunately, for most applications, there is insufficient mechanistic knowledge of underlying virus structure-function relationships to empower rational design improvements.
As an alternative, for over two decades we have been implementing directed evolution – the iterative genetic diversification of the viral genome and functional selection for desired properties – to engineer highly optimized, next generation AAV variants for efficient and targeted delivery to any cell or tissue target. We have genetically diversified AAV using a broad range of approaches, and the resulting large (~109) libraries are then functionally selected for substantially enhanced delivery in small and large animal models. Furthermore, our vector engineering process has more recently been enhanced through next generation sequencing and machine learning. The resulting variants have been effective in both animal models and in 6 human clinical trials to date, and results from both will be discussed.
RESEARCH
The Schaffer research group employs molecular and cellular engineering approaches to investigate biomedical problems. They are interested in the related areas of stem cell bioengineering, gene delivery systems, and molecular virology, with applications in regenerative medicine and tissue engineering. One their our major research aims is dedicated to understanding the biology and exploring the therapeutic potential of gene delivery, which serves as an effective means to control stem cells. Gene therapy can be defined as the introduction of genetic material to the cells of an individual for therapeutic benefit. A variety of approaches are under development to use gene therapy for treating cancer, AIDS, and a number of inherited genetic disorders. For example, gene therapy could be used to replace the genes hemophilia patients are missing, to bolster the immune system to recognize and combat tumors, or to inhibit the replication of HIV virus. However, significant progress must still be made before these developing strategies become therapeutic realities. One of the most formidable obstacles to gene therapy is how to efficiently deliver genes to a sufficient number of cells to yield a therapeutic effect. A number of gene delivery vehicles, or vectors, are in development, and most exploit or emulate the abilities many viruses have evolved to deliver their genes to cells as part of their life cycles. However, while viruses have developed numerous strategies to deliver genes over millions of years of evolution, the efficiency and safety of vehicles based upon recombinant viruses must still be further improved. The Schaffer lab has developed numerous high-throughput directed evolution approaches to engineer the properties of viral vehicles at the molecular level to enhance their abilities to deliver genes. These successful efforts are enhancing the abilities of several vectors to make them more effective at delivering gene “medicines.”
View Full 2025-2026 Bioengineering Seminar Series Schedule
