Plenary Keynote Program

Join 1,100+ of your colleagues for the Discovery on Target Plenary Keynote Program. Bridging both halves of the event, it's the only time our whole community of drug discovery professionals assembles in one room to learn about big-picture perspectives, innovative technologies, and thought-provoking trends from luminaries in the field.

 

Last year's 2019 Plenary Keynote Program featured:

Base Editing: Chemistry on a Target Nucleotide in the Genome of Living Cells

David R. Liu, PhD, Howard Hughes Medical Institute Investigator, Professor of Chemistry & Chemical Biology, Harvard University

Point mutations represent most known human genetic variants associated with disease but are difficult to correct cleanly and efficiently using standard nuclease-based genome editing methods. In this lecture I will describe the development, application, and evolution of base editing, a new approach to genome editing that directly converts a target base pair to another base pair in living cells without requiring double-stranded DNA breaks or donor DNA templates. Through a combination of protein engineering and protein evolution, we recently developed two classes of base editors (BE4 and ABE) that together enable all four types of transition mutations (C to T, T to C, A to G, and G to A) to be efficiently and cleanly installed or corrected at target positions in genomic DNA. The four transition mutations collectively account for most known human pathogenic point mutations. Base editing has been widely used by many laboratories around the world in a wide range of organisms including bacteria, fungi, plants, fish, mammals, and even human embryos. We have recently expanded the scope of base editing by enhancing its efficiency, product purity, targeting scope, and DNA specificity. By optimizing base editor expression, we developed “max” versions of cytosine and adenine base editors with greatly increased editing efficiency in mammalian cells. We also show that base editing can function in vivo in post-mitotic somatic cells that do not support homology-directed repair. To improve the targeting scope of base editing, we used our phage-assisted continuous evolution (PACE) system to rapidly evolve Cas9 and base editor variants with broadened PAM compatibility, higher DNA specificity, and enhanced editing capabilities. Finally, we integrated several of these developments to address cell and animal models of human genetic disease. Base editing can be used to correct pathogenic point mutations, introduce disease-suppressing mutations, and create new models of genetic diseases.

PROTACs: Past, Present, and Future

Craig M. Crews, PhD, Professor, Chemistry; Pharmacology; Molecular, Cellular & Developmental Biology; Yale University

The ability to control protein levels using PROTACs is changing how drugs are being developed and is expanding our concept of the druggable target space. Moreover, PROTACs offer the advantages of siRNA but with more favorable pharmaceutical properties (ADME, biodistribution, routes of administration). For the past 18 years, Professor Crews has pioneered the development of this new modality from concept to clinical trials. Here he will describe the current and future trends in this fast-paced, exciting new therapeutic field.

 

Past Plenary Keynote speakers have included:

Diversification of Antibody Effector Function

Jeffrey V. Ravetch, MD, PhD, The Rockefeller University

Ubiquitin- and ATP-Dependent Unfoldase Activity of p97/VCP•Npl4•Ufd1 Is Enhanced by Mutations that Cause Multisystem Proteinopathy

Raymond J. Deshaies, PhD, Amgen

Meeting the New Challenges of Novel Drug Development

Gregory L. Verdine, PhD, Harvard University and Harvard Medical School

Towards a Patient-Based Drug Discovery

Stuart L. Schreiber, PhD, Broad Institute of Harvard and MIT