# David R. Liu

David Ruchien Liu (Chinese: 劉如謙; pinyin: Liú Rúqiān; born 1973) is an American molecular biologist and organic chemist who is the Thomas Dudley Cabot Professor of the Natural Sciences at Harvard University and the Richard Merkin Professor at the Broad Institute, where he is the director of the Merkin Institute for Transformative Technologies.
As an undergraduate at Harvard, Liu worked with Nobel Prize laureate Elias James Corey and graduated first in his class. After earning his Ph.D. from the University of California, Berkeley, Liu was made an assistant professor at Harvard at age 26.

## Early life and education

Liu was born to a Taiwanese American family in Riverside, California, on June 12, 1973. Both of his parents immigrated to the United States from Taiwan. His father is an aerospace engineer and his mother is a retired physics professor at the University of California, Riverside. As a child, Liu developed an interest in science after playing with insects in his backyard. He attended Riverside Polytechnic High School in 1990 and graduated as class valedictorian. While in high school, he finished second in the 1990 national Westinghouse Science Talent Search.
After high school, Liu entered Harvard University, where he excelled academically and graduated in 1994 with a Bachelor of Arts (B.A.) in chemistry, summa cum laude, ranked first out of the 1,641 students at Harvard College. As an undergraduate, he worked in the synthetic chemistry laboratory of Nobel laureate Elias James Corey and was elected to Phi Beta Kappa. Liu was awarded Harvard's 1994 Thomas T. Hoopes Prize for an outstanding senior thesis titled, "Studies on 2,3-Oxidosqualene Cyclase: A Synthetic and Molecular Biological Approach", and shared the prize with Corey. For being the highest ranking member of Harvard's undergraduate class, the university also awarded Liu its Sophia Freund Prize.
Liu was the lead tester of Naughty Dog's 1994 video game Way of the Warrior, for which he also provided the voice of the character Chin "The Dragon" Liu. He was known to be a prolific professional Street Fighter II player, with Naughty Dog co-founder Andy Gavin saying that "He was one of those savant guys at Street Fighter who’s just insanely good". Liu would attempt to plug Way of the Warrior during television interviews about his time in Harvard.
After graduating from Harvard, Liu received a Department of Defense National Defense Science and Engineering Graduate Fellowship and a fellowship from the Howard Hughes Medical Institute to pursue graduate studies at the University of California, Berkeley. Liu earned his Ph.D. from Berkeley in organic chemistry in 1999 under the supervision of chemist Peter G. Schultz.

## Academic career

After earning his Ph.D., Liu became an assistant professor of chemistry and chemical biology at Harvard at age 26. 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 270 papers and is the inventor of more than 110 issued U.S. patents. He 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. 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). He is the 2022 King Faisal Prize Laureate in Medicine, and the 2024 Jacob and Louise Gabbay Award recipient.

## 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. DNA-Templated Synthesis (DTS) generated some of the first examples of DNA-encoded libraries (DELs), now commonly used in drug discovery efforts in academia and in pharmaceutical companies.
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. He has published over 270 peer-reviewed publications and his H-index is ≥150 according to Google Scholar.

## 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), Resonance Medicine (novel enzymatic solutions for unmet challenges in medicine), and nChroma Bio (novel gene editing delivery technologies and genomic medicines that harness epigenetics). 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.

## Personal life

Liu met his wife, Julie Liu, while attending the University of California, Berkeley.

## Selected papers

* Gartner, ZJ; Liu, DR (July 2001). "The generality of DNA-templated synthesis as a basis for evolving non-natural small molecules". J. Am. Chem. Soc. 123 (28): 6961–3. Bibcode:2001JAChS.123.6961G. doi:10.1021/ja015873n. PMC 2820563. PMID 11448217.
* Kanan, MW; Rozenman, MM; Sakurai, K; Snyder, TM; Liu, DR (2004). "Reaction discovery enabled by DNA-templated synthesis and in vitro selection". Nature. 431 (7008): 545–9. Bibcode:2004Natur.431..545K. doi:10.1038/nature02920. PMC 2814052. PMID 15457254.
* Gartner, ZJ; Tse, BN; Grubina, R; Doyon, JB; Snyder, TM; Liu, DR (September 2004). "DNA-templated organic synthesis and selection of a library of macrocycles". Science. 305 (5690): 1601–5. Bibcode:2004Sci...305.1601G. doi:10.1126/science.1102629. PMC 2814051. PMID 15319493.
* Georghiou, G; Kleiner, RE; Pulkoski-Gross, M; Liu, DR; Seeliger, MA (2012). "Highly specific, bisubstrate-competitive Src inhibitors from DNA-templated macrocycles". Nature Chemical Biology. 8 (4): 366–74. doi:10.1038/nchembio.792. PMC 3307835. PMID 22344177.
* Cronican, JJ; Thompson, DB; Beier, KT; McNaughton, BR; Cepko, CL; Liu, DR (2010). "Potent delivery of functional proteins into Mammalian cells in vitro and in vivo using a supercharged protein". ACS Chem. Biol. 5 (8): 747–52. doi:10.1021/cb1001153. PMC 2924640. PMID 20545362.
* Komor, AC; Kim, YB; Packer, MS; Zuris, JA; Liu, DR (19 May 2016). "Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage". Nature. 533 (7603): 420–4. Bibcode:2016Natur.533..420K. doi:10.1038/nature17946. PMC 4873371. PMID 27096365.
* Kim, YB; Komor, AC; Levy, JM; Packer, MS; Zhao, KT; Liu, DR (April 2017). "Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions". Nature Biotechnology. 35 (4): 371–376. doi:10.1038/nbt.3803. PMC 5388574. PMID 28191901.
* Gaudelli, NM; Komor, AC; Rees, HA; Packer, MS; Badran, AH; Bryson, DI; Liu, DR (23 November 2017). "Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage". Nature. 551 (7681): 464–471. Bibcode:2017Natur.551..464G. doi:10.1038/nature24644. PMC 5726555. PMID 29160308.
* Lawrence, M. S.; Phillips, K. J.; Liu, D. R. (2007). "Supercharging Proteins Can Impart Extraordinary Resilience". J. Am. Chem. Soc. 129 (33): 10110–10112. doi:10.1021/ja071641y. PMC 2820565. PMID 17665911.
* McNaughton, B. R.; Cronican, J. J.; Liu, D. R. (2009). "Mammalian Cell Penetration, siRNA Transfection, and DNA Transfection by Supercharged Proteins". Proc. Natl. Acad. Sci. USA. 106 (15): 6111–6116. Bibcode:2009PNAS..106.6111M. doi:10.1073/pnas.0807883106. PMC 2659711. PMID 19307578.
* Esvelt, K. M.; Carlson, J. C.; Liu, D. R. (2011). "A System for the Continuous Directed Evolution of Biomolecules". Nature. 472 (7344): 499–503. Bibcode:2011Natur.472..499E. doi:10.1038/nature09929. PMC 3084352. PMID 21478873.
* Dickinson, B. C.; Leconte, A. M.; Allen, B.; Esvelt, K. M.; Liu, D. R. (2013). "Experimental Interrogation of the Path Dependence and Stochasticity of Protein Evolution Using Phage-Assisted Continuous Evolution". Proc. Natl. Acad. Sci. USA. 110 (22): 9007–9012. Bibcode:2013PNAS..110.9007D. doi:10.1073/pnas.1220670110. PMC 3670371. PMID 23674678.
* 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. (2014). "Anti-Diabetic Activity of Insulin-Degrading Enzyme Inhibitors Mediated by Multiple Hormones". Nature. 511 (7507): 94–98. Bibcode:2014Natur.511...94M. doi:10.1038/nature13297. PMC 4142213. PMID 24847884.
* Zuris, J. A.; Thompson, D. B.; Shu, Y.; Guilinger, J. P.; Bessen, J. L.; Hu, J. H.; Maeder, M. L.; Joung, J. K.; Chen, Z.-Y.; Liu, D. R. (2015). "Cationic Lipid-Mediated Delivery of Proteins Enables Efficient Protein-Based Genome Editing In Vitro and In Vivo". Nat. Biotechnol. 33 (1): 73–80. doi:10.1038/nbt.3081. PMC 4289409. PMID 25357182.
* Badran, A. H.; Guzov, V. M.; Huai, Q.; Kemp, M. M.; Vishwanath, P.; Kain, W.; Evdokimov, A.; Moshiri, F.; Turner, K. H.; Wang, P.; Malvar, T.; Liu, D. R. (2016). "Continuous Evolution of B. thuringiensis Toxins Overcomes Insect Resistance". Nature. 533 (7601): 58–63. doi:10.1038/nature17938. PMC 4865400. PMID 27120167.
* Gao, X.; Lamas, V.; Huang, M.; Yeh, W.-H.; Pan, B.; Hu, Y.-J.; Hu, J. H.; Thompson, D. B.; Shu, Y.; Li, Y.; Wang, H.; Yang, S.; Xu, Q.; Polley, D. B.; Liberman, M. C.; Kong, W.-J.; Holt, J. R.; Chen, Z.-Y.; Liu, D. R. (2018). "Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents". Nature. 553 (7687): 217–221. Bibcode:2018Natur.553..217G. doi:10.1038/nature25164. PMC 5784267. PMID 29258297.
* Tang, W; Liu, D.R. (2018). "Rewritable multi-event analog recording in bacterial and mammalian cells". Science. 360 (6385): eaap8992. doi:10.1126/science.aap8992. PMC 5898985. PMID 29449507.
* Hu, J. H.; Miller, S. M.; Geurts, M. H.; Tang, W.; Chen, L.; Sun, N.; Zeina, C.; Gao, X.; Rees, H. A.; Lin, Z.; Liu, D. R. (2018). "Evolved Cas9 Variants with Broad PAM Compatibility and High DNA Specificity". Nature. 556 (7699): 57–63. Bibcode:2018Natur.556...57H. doi:10.1038/nature26155. PMC 5951633. PMID 29512652.
* 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