Britton Chance Distinguished Lecture in Engineering and Medicine

David Schaffer2018 Lecture

David Schaffer
Professor of Chemical and Biomolecular Engineering
University of California at Berkeley

“Directed Evolution of New Viruses for Therapeutic Gene Delivery”

Wednesday, November 17, 2018, 3:00 PM, Wu and Chen Auditorium, Levine Hall

Abstract:
Gene therapy has experienced an increasing number of successful human clinical trials – particularly ones using delivery vehicles or vectors based on adeno-associated viruses (AAV) – including trials for hemophilia B, Leber’s congenital amaurosis (LCA2), and spinal muscular atrophy.  This progress recently led to the first FDA approval of an AAV-based gene therapy (for LCA2) in December 2017.  These clear successes have been made possible by the identification of disease targets that are suitable for the delivery properties of natural variants of AAV.  However, vectors, in general, face a number of barriers and challenges that limit their efficacy for other disease targets, including pre-existing antibodies against AAVs, suboptimal biodistribution, limited spread within tissues, an inability to target delivery to specific cells, and/or limited delivery efficiency to target 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, we were the first to develop and, have since 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 delivery to any cell or tissue target.  We have genetically diversified AAV using a broad range of approaches, including random point mutagenesis of the cap gene, insertion of random peptide sequences into the AAV capsid, recombination of cap genes from a number of parental serotypes to create random chimeras, and construction of ancestral AAV libraries.  The resulting large (~109) libraries are then phenotypically selected for improved function in small and large animal models, yielding AAVs capable of highly efficient and targeted delivery in vivo and thereby laying a foundation for translating engineered AAVs into human clinical trials.

Speaker Biography:
David Schaffer is a Professor of Chemical and Biomolecular Engineering, Bioengineering, and Neuroscience at the University of California at Berkeley, where he also serves as the Director of the Berkeley Stem Cell Center. He received a B.S. in Chemical Engineering from Stanford University in 1993 and a Ph.D. in Chemical Engineering from MIT in 1998. He then conducted a postdoctoral fellowship at the Salk Institute for Biological Studies, before joining the University of California at Berkeley in 1999. There, he applies engineering principles to enhance stem cell and gene therapies; work that includes novel approaches for molecular engineering and evolution of new viral vectors, as well as new technologies to investigate and control stem cell fate decisions.

David Schaffer has received an NSF CAREER Award, Office of Naval Research Young Investigator Award, Whitaker Foundation Young Investigator Award, and was named a Technology Review Top 100 Innovator. He was also awarded the American Institute of Chemical Engineers Pharmaceutical and Bioengineering Award in 2017, the American Chemical Society Marvin Johnson Award in 2016, the American Chemical Society BIOT Division Young Investigator Award in 2006, the Biomedical Engineering Society Rita Shaffer Young Investigator Award in 2000, and was inducted into the College of Fellows of the American Institute of Medical and Biological Engineering in 2010.

Previous Britton Chance Distinguished Lecturers

1995: Lewis S. Edelheit, General Electric Company

1996: Douglas A. Lauffenburger, Massachusetts Institute of Technology

1998: George Georgiou, University of Texas at Austin

1999: Jeffrey A. Hubbell, University of Zürich

2000: W. Mark Saltzman, Cornell University

2001: Chaitan S. Khosla, Stanford University

2002: Sangtae Kim, Lilly Research Laboratories

2003: Larry V. McIntire, Rice University

2004: Deborah E. Leckband, University of Illinois at Urbana-Champaign

2004: Stephen R. Quake, Stanford University

2005: Frances H. Arnold, California Institute of Technology

2006: Adam P. Arkin, University of California at Berkeley

2007: Kristi S. Anseth, University of Colorado at Boulder

2008: Jay D. Keasling, University of California at Berkeley

2009: Mark E. Davis, California Institute of Technology

2010: David A. Tirrell, California Institute of Technology

2011: Frank S. Bates, University of Minnesota

2012: Arup K. Chakraborty, Massachusetts Institute of Technology

2013: Melody A. Swartz, Ecole polytechnique federale de Lausanne

2014: James C. Liao, University of California, Los Angeles

2015: Samir Mitragotri, University of California, Santa Barbara

2016: David Mooney, Harvard School of Engineering and Applied Science

2017: Lynda G. Griffith, Massachusetts Institute of Technology

This distinguished lecture honors Britton Chance

Britton ChanceBritton Chance (1913-2010) was a world leader in transforming theoretical science into useful biomedical and clinical applications. Among his pioneering contributions to fundamental biomedical science were his discovery of numerous enzyme-substrate compounds, World War II development of computers for Radar, the elucidation of the fundamental principles of control of bioenergetics and metabolism, the first human subject study using 31P NMR (phosphorous nuclear magnetic resonance) spectroscopy and more recently optical spectroscopy and imaging of human brain and breast. Through decades of scholarly mentorship of colleagues in disciplines ranging from mathematics to clinical medicine, he brought additional distinction to this University and multiplied its contributions to improving the human condition.

Professor Chance was Eldridge Reeves Johnson University Professor of Biophysics, Physical Chemistry and Radiologic Physics at Penn. He received his undergraduate degree from Penn’s Towne Scientific School in 1935 and doctoral degrees from both Penn and the University of Cambridge. He was a member of the National Academy of Sciences and of the Institute of Medicine and a Foreign Member of the Royal Society of London. Among very many other recognitions, he received the National Medal of Science, the Benjamin Franklin Medal from the American Philosophical Society, the Biological Physics Prize from the American Physical Society, and honorary degrees from the Karolinska Institut, the Medical College of Ohio at Toledo, Semmelweis University, Hahnemann Medical College and the Universities of Pennsylvania, Helsinki, Dusseldorf and Buenos Aires. In his honor, Huazhong University of Science and Technology named a major laboratory as the Britton Chance Center for Biomedical Photonics.