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
Hubbard Howe Professor of Chemical and Biomolecular Engineering, Bioengineering, and Molecular and Cell Biology
University of California, Berkeley

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ABSTRACT
Gene therapy has experienced an increasing number of successful human clinical trials, leading to 6 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 were sufficient. However, vectors face a number of barriers and shortcomings that preclude their extension to most human diseases, including limited delivery efficiency 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 from fully random (e.g. error prone PCR) to computationally guided (e.g. by machine learning). The resulting large (~109) libraries are then functionally selected for substantially enhanced delivery, yielding AAVs capable of highly efficient therapeutic gene delivery. Our variants have been effective in both animal models and in 6 human clinical trials to date, and results from both will be discussed.

BIO
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 Executive Director of QB3 and the Director of the Bakar Bioenginuity Hub and Bakar Labs. He received a B.S. from Stanford University in 1993 and a Ph.D. from MIT in 1998, both in chemical engineering. He then conducted a postdoctoral fellowship at the Salk Institute for Biological Studies before joining Berkeley in 1999. There, he applies engineering principles to optimize gene and stem cell therapies, work that includes developing the concept of applying directed evolution to engineer targeted and efficient viral gene therapy vectors as well as new technologies to investigate and control stem cell fate decisions. He has published >240 papers, has advised >90 graduate students and postdoctoral fellows, is an inventor on >50 patents, and developed technologies that are being used in 8 human clinical trials. In addition, he has co-founded eight companies, including 4D Molecular Therapeutics (NASDAQ FDMT), Ignite Immunotherapies (acquired by Pfizer) and Rewrite (acquired by Intellia). Finally, he has received recognitions including the National Academy of Inventors, Andreas Acrivos Professional Progress Award, the American Institute of Chemical Engineers Pharmaceutical and Bioengineering Award, the American Chemical Society Marvin Johnson Award, and the Biomedical Engineering Society Rita Shaffer Young Investigator Award.