David Schaffer seminar (Fredrickson Lecture)
Professor of Chemical and Biomolecular Engineering, Bioengineering, and Molecular and Cell Biology at the University of California, Berkeley, David Schaffer, will deliver this year's Fredrickson Lecture, titled, "Directed Evolution of New AAV Vectors for Clinical Gene Therapy," on Thursday, April 23rd at 1:25 p.m. in room B75 Amundson Hall.
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.
Biography
David Schaffer is the Hubbard Howe Professor of Chemical and Biomolecular Engineering, Bioengineering, and Molecular and Cell Biology at the University of California, Berkeley, and he also serves as the Director of QB3 and the Director of the Bakar Labs, Bakar Bio Labs, Bakar Climate Labs, and the Bakar Fellows Program. He received a B.S. from Stanford University in 1993 and a Ph.D. from MIT in 1998, both in chemical engineering.
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.
Biography
David Schaffer is the Hubbard Howe Professor of Chemical and Biomolecular Engineering, Bioengineering, and Molecular and Cell Biology at the University of California, Berkeley, and he also serves as the Director of QB3 and the Director of the Bakar Labs, Bakar Bio Labs, Bakar Climate Labs, and the Bakar Fellows Program. He received a B.S. from Stanford University in 1993 and a Ph.D. from MIT in 1998, both in chemical engineering.
