David Liu

Professor of Chemistry and Chemical Biology

12 Oxford Street
Department of Chemistry and Chemical Biology
Harvard University
Cambridge, MA 02138
Tel: 617-496-1067
Email: drliu@chemistry.harvard.edu

Website:
http://evolve.harvard.edu/
Lab Size: Greater than 20

Summary

Over the past five years, we initiated a new research effort to understand, develop, and apply genome-editing agents with the potential to treat human genetic diseases (Area 1). This effort synergizes with two other areas of ongoing research in our group: the development and application of phage-assisted continuous evolution (PACE) (Area 2), and methods to deliver proteins into mammalian cells in vivo (Area 3). In addition, we deepened our use of DNA-templated synthesis (DTS) to discover bioactive molecules that illuminate biology and validate new therapeutic targets (Area 4). We have achieved major advances in each of these areas over the past five years, including the development of base editing, a new approach to genome editing that directly converts one DNA base pair to another base pair without inducing double-stranded DNA cleavage (Nature 533, 420 (2016)); the development of PACE (Nature 472, 499 (2011)) and its application to address a major problem facing modern agriculture (Nature 533, 58 (2016)); the development of a new protein delivery method that enables virus- and plasmid-free genome editing in vivo (Nature Biotechnology 33, 73 (2015)); and the discovery of the first physiologically active inhibitor of the enzyme that degrades insulin in humans (Nature 511, 94 (2014)).

See http://evolve.harvard.edu/2016ResearchSummary.pdf for details, and http://evolve.harvard.edu for our group website.

Publications

“A System for the Continuous Directed Evolution of Biomolecules” Esvelt, K. M.; Carlson, J. C.; Liu, D. R. Nature 472, 499–503 (2011). 

“Highly Specific, Bisubstrate-Competitive Src Inhibitors From DNA-Templated Macrocycles” Georghiou, G.; Kleiner, R. E.; Pulkoski-Gross, M.; Liu, D. R.; Seeliger, M. A. Nature Chemical Biology 8, 366-374 (2012).

“Comprehensive Off-Target DNA Cleavage Profiling Reveals RNA-Programmed Cas9 Nuclease Specificity” Pattanayak, V.; Lin, S.; Guilinger, J.P.; Ma, E.; Doudna, J. A.; Liu, D. R. Nature Biotechnology in press (2013).

“Enzyme-Free Translation of DNA into Sequence-Defined Synthetic Polymers Structurally Unrelated to Nucleic Acids” Niu, J.; Hili, R.; Liu, D. R. Nature Chemistry 5, 282-292 (2013).

“Engineering, Identifying, and Applying Supercharged Proteins for Macromolecule Delivery into Mammalian Cells” Thompson, D. B.; Cronican, J. J.; Liu, D. R. Methods in Enzymology 503, 293-319 (2012).