Directed Evolution of Next-Generation AAV Vector Systems for Clinical Gene Therapy

Presented at: BioProcessing 2020
C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Professor of Chemical and Biomolecular Engineering, University of California, Berkeley
    Biography
      David Schaffer is the Hubbard Howe Professor of Chemical and Biomolecular Engineering, Bioengineering, and Neuroscience at the University of California, Berkeley, where he also serves as the Director of the Berkeley Stem Cell Center. He received a B.S. from Stanford University in 1993 and a Ph.D. from MIT in 1998. He then conducted a postdoctoral fellowship at the Salk Institute for Biological Studies before joining the 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. He has published >200 papers, is an inventor on >50 patents, and has received recognitions including the American Institute of Chemical Engineers Pharmaceutical and Bioengineering Award, the American Chemical Society Marvin Johnson Award, the ACS BIOT Division Young Investigator Award, and the Biomedical Engineering Society Rita Shaffer Young Investigator Award.

    Abstract

    There has been an increasing number of successful gene therapy clinical trials, leading to regulatory approvals of numerous gene therapy products, in particular ones based on the adeno-associated virus (AAV).  That said, vectors based on natural versions of AAV face a number of delivery challenges that limit their efficacy and will thus preclude the extension of these successes to the majority of human diseases.  These delivery limitations arise since the parent viruses upon which these vectors are based were not evolved by nature for our convenience to use as human therapeutics.  We have been developing and implementing a high throughput approach termed directed evolution – involving the iterative genetic diversification of a viral genome and functional selection for desired properties – to engineer highly optimized variants of AAV for a broad range of cell and tissue targets.

    In parallel, the advent of genome editing technologies such as the CRISPR/Cas9 system raise the possibility of using gene delivery not only for gene replacement but for repair or knockout of endogenous genes.  We have thus been combining engineered AAVs with CRISPR/Cas9 for a range of applications, in particular, to treat central nervous system disorders.  The integration of these new technologies – Cas9 cargo with AAV delivery – can enable a broad range of basic and therapeutic applications.

    Learning Objectives:

    1. To gain an understanding of how preclinical and clinical research in gene therapy is leading to strong advances and clinical approvals

    2. To discuss how improvements in delivery technologies, such as engineered AAV delivery vectors, are still needed to fully unlock the potential of gene therapy and genome editing


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