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David Ruchien Liu (born 1973) is an American chemist and biologist. He is the Richard Merkin Professor, Director of the Merkin Institute of Transformative Technologies in Healthcare, and Vice-Chair of the Faculty at the Broad Institute of Harvard and MIT; Thomas Dudley Cabot Professor of the Natural Sciences and Professor of Chemistry and Chemical Biology at Harvard University; and Howard Hughes Medical Institute Investigator.

Early life and education

Liu was born in Riverside, California on June 12, 1973. Both his parents immigrated to the United States from Taiwan. His father is an aerospace engineer; his mother is a retired physics professor at U. C. Riverside. While in high school, he finished second in the 1990 national Westinghouse Science Talent Search. He received a B.A. in chemistry from Harvard in 1994, graduating summa cum laude and first in his class. While an undergraduate, he worked in the synthetic chemistry laboratory of Nobel Laureate E.J. Corey. Liu received his Ph.D. from UC Berkeley in Organic Chemistry in 1999, supervised by Peter G. Schultz.

Academic career

Liu graduated first in his class at Harvard in 1994. He performed organic and bioorganic chemistry research on sterol biosynthesis under Professor E. J. Corey's guidance as an undergraduate. During his Ph.D. research with Professor Peter Schultz at U. C. Berkeley, Liu initiated the first general effort to expand the genetic code in living cells. He earned his Ph.D. in 1999 and became assistant professor of chemistry and chemical biology at Harvard University in the same year. He was promoted to associate professor in 2003 and to full professor in 2005. Liu became a Howard Hughes Medical Investigator in 2005 and joined the JASONs, academic science advisors to the U.S. government, in 2009. He was honored as a Harvard College Professor in 2007, in part for his undergraduate teaching. His introductory life sciences course, beginning in 2005, became Harvard's largest natural sciences course.

Liu has earned several university-wide distinctions for teaching at Harvard, including the Joseph R. Levenson Memorial Teaching Prize, the Roslyn Abramson Award, and a Harvard College Professorship. Liu has published more than 165 papers and is the inventor of more than 60 issued U.S. patents. His research accomplishments have earned distinctions including the Ronald Breslow Award for Biomimetic Chemistry, the American Chemical Society Pure Chemistry Award, the Arthur C. Cope Young Scholar Award, and awards from the Sloan Foundation, Beckman Foundation, NSF CAREER Program, and Searle Scholars Program. In 2016 he was named one of the Top 20 Translational Researchers in the world by Nature Biotechnology, and in 2017 and 2019 was named to the Nature’s 10 researchers in world and to the Foreign Policy Leading Global Thinkers. In April, 2019, Liu delivered a TED talk on base editing in Vancouver at TED2019, resulting in a standing ovation from the live audience. In 2019, prime editing was named as one of Nature's 10 remarkable papers from 2019 and one of The Scientist's top technical advances. In 2020, Liu earned the American Chemical Society David Perlman Award and the American Chemical Society ACS Chemical Biology Lectureship Award, was elected to the National Academy of Science (NAS), the National Academy of Medicine (NAM) and was named as a Fellow of the American Association for the Advancement of Science (AAAS).

Research

Liu's research group pioneered base editing, a new method of genome editing that enables the direct and precise conversion of a single base to another base in the genome of living cells, without making DNA double-stranded breaks (DSBs) that lead to complex mixtures of insertions, deletions, and DNA rearrangements. Liu's research group also pioneered prime editing, a versatile genome editing method that can install all possible base-to-base conversions, insertions, deletions, and combinations in mammalian cells without requiring double-strand DNA breaks or donor DNA templates. Additionally, Liu's group developed DNA-templated synthesis (DTS), a technique to translate DNA sequences into synthetic small molecules, rather than proteins, and applied DTS to the discovery of bioactive small molecules and new chemical reactions. His lab also developed phage-assisted continuous evolution (PACE), a technique that uses the short 10-minute lifespan of M13 bacteriophage to achieve the rapid evolution of useful proteins. The lab has used PACE and its directed evolution efforts to generate new genome editing tools that allow for expanded DNA accessibility and DNA base conversions.

Commercial activity

Liu co-founded Editas Medicine (genome editing with CRISPR nucleases for human therapeutics), Pairwise Plants (genome editing for agriculture), Beam Therapeutics (base editing for human therapeutics), Exo Therapeutics (novel small-molecule drug discovery). He is the scientific founder of Prime Medicine (prime editing for human therapeutics).

Liu also founded Permeon Biologics and Ensemble Therapeutics. Permeon Biologics was founded in 2011 by Liu and Flagship Ventures to develop a class of proteins to enable the transport of large molecules such as antibodies into cells to facilitate development of "intrabody" therapeutics and ceased its operations in 2015. Ensemble Therapeutics was founded in 2004 with funding from Flagship Ventures to develop Liu's work on macrocycles; the company raised about $40M and struck several pharmaceutical partnerships, but was shut down in 2017 before any of its lead compounds had reached the market.

Selected papers

• ZJ Gartner, DR Liu: The generality of DNA-templated synthesis as a basis for evolving non-natural small molecules. In: J. Am. Chem. Soc.. 123, Nr. 28, July 2001, S. 6961–3. . PMID 11448217. PMC 2820563 (freier Volltext).
• MW Kanan, MM Rozenman, K Sakurai, TM Snyder, DR Liu: Reaction discovery enabled by DNA-templated synthesis and in vitro selection. In: Nature. 431, Nr. 7008, 2004, S. 545–9. bibcode:2004Natur.431..545K. . PMID 15457254. PMC 2814052 (freier Volltext).
• ZJ Gartner, BN Tse, R Grubina, JB Doyon, TM Snyder, DR Liu: DNA-templated organic synthesis and selection of a library of macrocycles. In: Science. 305, Nr. 5690, September 2004, S. 1601–5. bibcode:2004Sci...305.1601G. . PMID 15319493. PMC 2814051 (freier Volltext).
• G Georghiou, RE Kleiner, M Pulkoski-Gross, DR Liu, MA Seeliger: Highly specific, bisubstrate-competitive Src inhibitors from DNA-templated macrocycles. In: Nature Chemical Biology. 8, Nr. 4, 2012, S. 366–74. . PMID 22344177. PMC 3307835 (freier Volltext).
• JJ Cronican, DB Thompson, KT Beier, BR McNaughton, CL Cepko, DR Liu: Potent delivery of functional proteins into Mammalian cells in vitro and in vivo using a supercharged protein. In: ACS Chem. Biol.. 5, Nr. 8, 2010, S. 747–52. . PMID 20545362. PMC 2924640 (freier Volltext).
• AC Komor, YB Kim, MS Packer, JA Zuris, DR Liu: Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage.. In: Nature. 533, Nr. 7603, 19 May 2016, S. 420–4. bibcode:2016Natur.533..420K. . PMID 27096365. PMC 4873371 (freier Volltext).
• YB Kim, AC Komor, JM Levy, MS Packer, KT Zhao, DR Liu: Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions.. In: Nature Biotechnology. 35, Nr. 4, April 2017, S. 371–376. . PMID 28191901. PMC 5388574 (freier Volltext).
• NM Gaudelli, AC Komor, HA Rees, MS Packer, AH Badran, DI Bryson, DR Liu: Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage.. In: Nature. 551, Nr. 7681, 23 November 2017, S. 464–471. bibcode:2017Natur.551..464G. . PMID 29160308. PMC 5726555 (freier Volltext).
• M. S. Lawrence, K. J. Phillips, D. R. Liu: Supercharging Proteins Can Impart Extraordinary Resilience. In: J. Am. Chem. Soc.. 129, Nr. 33, 2007, S. 10110–10112. . PMID 17665911. PMC 2820565 (freier Volltext).
• B. R. McNaughton, J. J. Cronican, D. R. Liu: Mammalian Cell Penetration, siRNA Transfection, and DNA Transfection by Supercharged Proteins. In: Proc. Natl. Acad. Sci. USA. 106, Nr. 15, 2009, S. 6111–6116. bibcode:2009PNAS..106.6111M. . PMID 19307578. PMC 2659711 (freier Volltext).
• K. M. Esvelt, J. C. Carlson, D. R. Liu: A System for the Continuous Directed Evolution of Biomolecules. In: Nature. 472, Nr. 7344, 2011, S. 499–503. bibcode:2011Natur.472..499E. . PMID 21478873. PMC 3084352 (freier Volltext).
• B. C. Dickinson, A. M. Leconte, B. Allen, K. M. Esvelt, D. R. Liu: Experimental Interrogation of the Path Dependence and Stochasticity of Protein Evolution Using Phage-Assisted Continuous Evolution. In: Proc. Natl. Acad. Sci. USA. 110, Nr. 22, 2013, S. 9007–9012. bibcode:2013PNAS..110.9007D. . PMID 23674678. PMC 3670371 (freier Volltext).
• J. P. Maianti, A. McFedries, Z. H. Foda, R. E. Kleiner, X.-Q. Du, M. A. Leissring, W.-J. Tang, M. J. Charron, M. A. Seeliger, A. Saghatelian, D. R. Liu: Anti-Diabetic Activity of Insulin-Degrading Enzyme Inhibitors Mediated by Multiple Hormones. In: Nature. 511, Nr. 7507, 2014, S. 94–98. bibcode:2014Natur.511...94M. . PMID 24847884. PMC 4142213 (freier Volltext).
• J. A. Zuris, D. B. Thompson, Y. Shu, J. P. Guilinger, J. L. Bessen, J. H. Hu, M. L. Maeder, J. K. Joung, Z.-Y. Chen, D. R. Liu: Cationic Lipid-Mediated Delivery of Proteins Enables Efficient Protein-Based Genome Editing In Vitro and In Vivo. In: Nat. Biotechnol.. 33, Nr. 1, 2015, S. 73–80. . PMID 25357182. PMC 4289409 (freier Volltext).
• A. H. Badran, V. M. Guzov, Q. Huai, M. M. Kemp, P. Vishwanath, W. Kain, A. Evdokimov, F. Moshiri, K. H. Turner, P. Wang, T. Malvar, D. R. Liu: Continuous Evolution of B. thuringiensis Toxins Overcomes Insect Resistance. In: Nature. 533, Nr. 7601, 2016, S. 58–63. . PMID 27120167. PMC 4865400 (freier Volltext).
• X. Gao, V. Lamas, M. Huang, W.-H. Yeh, B. Pan, Y.-J. Hu, J. H. Hu, D. B. Thompson, Y. Shu, Y. Li, H. Wang, S. Yang, Q. Xu, D. B. Polley, M. C. Liberman, W.-J. Kong, J. R. Holt, Z.-Y. Chen, D. R. Liu: Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents. In: Nature. 553, Nr. 7687, 2018, S. 217–221. bibcode:2018Natur.553..217G. . PMID 29258297. PMC 5784267 (freier Volltext).
• W Tang, D.R. Liu: Rewritable multi-event analog recording in bacterial and mammalian cells. In: Science. 360, Nr. 6385, 2018. . PMID 29449507. PMC 5898985 (freier Volltext).
• J. H. Hu, S. M. Miller, M. H. Geurts, W. Tang, L. Chen, N. Sun, C. Zeina, X. Gao, H. A. Rees, Z. Lin, D. R. Liu: Evolved Cas9 Variants with Broad PAM Compatibility and High DNA Specificity. In: Nature. 556, Nr. 7699, 2018, S. 57–63. bibcode:2018Natur.556...57H. . PMID 29512652. PMC 5951633 (freier Volltext).
• Maianti, J. P.; McFedries, A.; Foda, Z. H.; Kleiner, R. E.; Du, X.-Q.; Leissring, M. A.; Tang, W.-J.; Charron, M. J.; Seeliger, M. A.; Saghatelian, A.; Liu, D. R. Nature 511, 94-98 (2014). “Anti-Diabetic Activity of Insulin-Degrading Enzyme Inhibitors Mediated by Multiple Hormones” PMC4142213
• Anzalone, A.V.; Randolph, P.B.; Davis, J.R.; Sousa, A.A.; Koblan, L.W.; Levy, J.M.; Chen, P.J.; Wilson, C.; Newby, G.A.; Raguram, A.; Liu, D.R. Nature,  576, 149–157 (2019). “Search-and-replace genome editing without double-strand breaks or donor DNA.”  PMCID: PMC6907074
• Mok, B. Y; de Moraes, M. H; Zeng, J; Bosch, D. E; Kotrys, A. V; Raguram, A.; Hsu, F; Radey, M.C; Broko Peterson, B; Mootha, V.K; Mougous, J.D;  Liu, D. R. Nature. available online (2020). "An interbacterial cytidine deaminase toxin enables mitochondrial base editing." PMCID: PMC7381381

See also

• DNA‐Templated Organic Synthesis

References

Vorlage:Reflist {{authority control}} {{ACS Chemical Biology Lectureship}} {{DEFAULTSORT:Liu, David R.}} [[Category:Living people]] [[Category:1973 births]] [[Category:21st-century American chemists]] [[Category:American people of Taiwanese descent]] [[Category:Harvard University faculty]] [[Category:Harvard University alumni]] [[Category:Howard Hughes Medical Investigators]] [[Category:UC Berkeley College of Chemistry alumni]] [[Category:Members of the United States National Academy of Sciences]]