David R. Liu

David Ruchien Liu (born 1973) is an American molecular biologist and chemist. 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.^[1]

David R. Liu
Liu in 2012
Born	(1973-06-12) June 12, 1973 (age 50) Riverside, California
Nationality	American
Alma mater	Harvard University (BA) University of California, Berkeley (PhD)
Known for	Nucleic acid templated chemistry directed evolution base editing prime editing
Scientific career
Institutions	Harvard University
Doctoral advisor	Peter G. Schultz
Other academic advisors	E.J. Corey
Chinese name
Traditional Chinese	劉如謙
Transcriptions Standard Mandarin Hanyu Pinyin Liú Rúqiān Wade–Giles Liu Ju-ch'ien

Early life and education

Liu was born in Riverside, California on June 12, 1973.^[2] Both his parents immigrated to the United States from Taiwan.^[3] His father is an aerospace engineer; his mother is a retired physics professor at the University of California, Riverside.^[2] While in high school, he finished second in the 1990 national Westinghouse Science Talent Search.^[4] He received his A.B. in chemistry from Harvard University 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.^[2][5] Liu received his Ph.D. in organic chemistry from the University of California, Berkeley in 1999,^[6] supervised by Peter G. Schultz.

Academic career

Liu graduated first in his class at Harvard in 1994.^[7] 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 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 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^[8] 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.^[9]

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 225 papers and is the inventor of more than 90 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.^[1] In April 2019, Liu delivered a TED talk on base editing in Vancouver at TED2019, resulting in a standing ovation from the live audience.^[10] 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),^[11] the National Academy of Medicine (NAM) and was named as a Fellow of the American Association for the Advancement of Science (AAAS). In 2022, he was awarded the King Faisal Prize in Medicine.^[12]

Research

Liu's research group pioneered base editing,^[13][14] 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.^[15] 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.^[16]

His lab also developed phage-assisted continuous evolution (PACE),^[17] 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.^[18] He has published over 230 peer-reviewed publications and his H-index is ≥130 according to Google Scholar.^[19]

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), Chroma Medicine (genomic medicines that harness epigenetics), Resonance Medicine (novel enzymatic solutions for unment challenges in medicine), and Nvelop Therapeutics (novel gene editing delivery technologies). 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.^[20] 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.^[21]

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. 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

See also

• DNA‐Templated Organic Synthesis

References

1. "David R. Liu". Liu Group. 2018-10-22. Retrieved 2019-04-02.
2. "Asian American: David Liu Speeds Up Evolution of Therapeutic Proteins". Goldsea Asian American Business: Asian Media Group. April 18, 2011.
3. Yang, Sophia (December 19, 2017). "Taiwanese-American named scientist of the yea... | Taiwan News". Taiwan News.
4. "Science Talent Search 1990". Society for Science. Retrieved 2023-04-18.
5. Bradt, Steve (2 June 2005). "Chemist, card shark Liu takes off". Harvard Gazette.
6. "CV". Google Docs. Retrieved 8 June 2021.
7. "David R. Liu". chemistry.harvard.edu. Retrieved 2019-04-02.
8. "David R. Liu, PhD Bio". HHMI. Retrieved 29 December 2017.^{[verification needed]}
9. Citation error. See inline comment how to fix.^{[verification needed]}
10. Liu, David R. (23 April 2019), Can we cure genetic diseases by rewriting DNA?, retrieved 2019-04-25
11. "News from the National Academy of Sciences". April 26, 2021. Retrieved July 4, 2021. Newly elected members and their affiliations at the time of election are: … Liu, David R.; investigator, Howard Hughes Medical Institute; and Thomas Dudley Cabot Professor of the Natural Sciences, department of chemistry and chemical biology, Harvard University, Cambridge, Mass., entry in member directory:"Member Directory". National Academy of Sciences. Retrieved July 4, 2021.
12. King Faisal Prize 2022
13. Komor, Alexis C.; Kim, Yongjoo B.; Packer, Michael S.; Zuris, John A.; Liu, David R. (May 2016). "Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage". Nature. 533 (7603): 420–424. Bibcode:2016Natur.533..420K. doi:10.1038/nature17946. ISSN 1476-4687. PMC 4873371. PMID 27096365.
14. Gaudelli, Nicole M.; Komor, Alexis C.; Rees, Holly A.; Packer, Michael S.; Badran, Ahmed H.; Bryson, David I.; Liu, David R. (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. ISSN 1476-4687. PMC 5726555. PMID 29160308.
15. Anzalone, Andrew V.; Randolph, Peyton B.; Davis, Jessie R.; Sousa, Alexander A.; Koblan, Luke W.; Levy, Jonathan M.; Chen, Peter J.; Wilson, Christopher; Newby, Gregory A.; Raguram, Aditya; Liu, David R. (2019-10-21). "Search-and-replace genome editing without double-strand breaks or donor DNA". Nature. 576 (7785): 149–157. Bibcode:2019Natur.576..149A. doi:10.1038/s41586-019-1711-4. ISSN 1476-4687. PMC 6907074. PMID 31634902.
16. Clark, Matthew A.; Liu, David R. (2009-02-08). "Design, synthesis and selection of DNA-encoded small-molecule libraries". Nature Chemical Biology. 5: 657–654. doi:10.5059/yukigoseikyokaishi.66.590.
17. Dickinson, Bryan C.; Leconte, Aaron M.; Allen, Benjamin; Esvelt, Kevin M.; Liu, David R. (2013-05-28). "Experimental interrogation of the path dependence and stochasticity of protein evolution using phage-assisted continuous evolution". Proceedings of the National Academy of Sciences. 110 (22): 9007–9012. Bibcode:2013PNAS..110.9007D. doi:10.1073/pnas.1220670110. ISSN 0027-8424. PMC 3670371. PMID 23674678.
18. Rees, Holly A.; Liu, David R. (December 2018). "Base editing: precision chemistry on the genome and transcriptome of living cells". Nature Reviews Genetics. 19 (12): 770–788. doi:10.1038/s41576-018-0059-1. ISSN 1471-0064. PMC 6535181. PMID 30323312.
19. "David R. Liu". Google Scholar. Retrieved 13 December 2022.
20. Brian Gormley, "Flagship Ventures Hatches Two More Health-Care Companies", The Wall Street Journal (March 17, 2011)
21. Keown, Alex (November 22, 2017). "Cambridge's Ensemble Therapeutics Quietly Shuts Down After 13 Years". BioSpace.